Page last updated: 2024-11-12

oligonucleotides

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID16133899
MeSH IDM0015278

Synonyms (5)

Synonym
acacccaattctgaaaatgg
antisense oligo to hiv-1 5349-5368
5'-acacccaattctgaaaatgg-3'
104053-06-7
oligonucleotides ,

Research Excerpts

Overview

Oligonucleotides (ONs) are a group of substances that display great therapeutic potential to interfere with gene expression. PBCA nanocapsules demonstrate to be a versatile delivery platform for small interfering RNA to treat a variety of diseases.

ExcerptReferenceRelevance
"Oligonucleotides is an emerging class of chemically-distinct therapeutic modalities, where extensive chemical modifications are fundamental for their clinical applications. "( Structurally constrained phosphonate internucleotide linkage impacts oligonucleotide-enzyme interaction, and modulates siRNA activity and allele specificity.
Alterman, JF; Aronin, N; Caiazzi, J; Conroy, F; Davis, SM; DiFiglia, M; Echeverria, D; Hassler, MR; Hildebrand, S; Khvorova, A; Miller, R; Pfister, EL; Roux, L; Sapp, E; Yamada, K, 2021
)
2.06
"Oligonucleotides are an emerging class of drugs that are manufactured by solid-phase synthesis. "( THERAPEUTIC OLIGONUCLEOTIDES, IMPURITIES, DEGRADANTS, AND THEIR CHARACTERIZATION BY MASS SPECTROMETRY.
Pourshahian, S, 2021
)
2.44
"As oligonucleotides are an ideal model system for small interfering RNA PBCA nanocapsules demonstrate to be a versatile delivery platform for small interfering RNA to treat a variety of diseases."( Pharmacokinetics on a microscale: visualizing Cy5-labeled oligonucleotide release from poly(n-butylcyanoacrylate) nanocapsules in cells.
Baier, G; Landfester, K; Mailänder, V; Tomcin, S, 2014
)
0.92
"DNA oligonucleotides are a very useful tool in biology. "( Seeds for effective oligonucleotide design.
Bigvand, AM; Ilie, L; Ilie, S; Khoshraftar, S, 2011
)
0.93
"Oligonucleotides (ONs) are a group of substances that display great therapeutic potential to interfere with gene expression."( Use of cell-penetrating-peptides in oligonucleotide splice switching therapy.
El Andaloussi, SA; Hammond, SM; Mäger, I; Wood, MJ, 2012
)
1.1
"Oligonucleotides (ONs) are an emerging class of drugs being developed for the treatment of a wide variety of diseases including the treatment of respiratory diseases by the inhalation route. "( Clinical expert panel on monitoring potential lung toxicity of inhaled oligonucleotides: consensus points and recommendations.
Alton, EW; Boushey, HA; Cavagnaro, J; Ferrari, N; Garn, H; Green, FH; Hodges, M; Johnson, G; Martin, RJ; Murdoch, RD; Parry, JD; Renz, H; Renzi, P; Seguin, R; Shrewsbury, SB; Tepper, J, 2012
)
2.05
"Oligonucleotides (ONs) are a new class of therapeutic compounds under investigation for the treatment of a variety of disease states, such as cancer and HIV, and for FDA approval of an anti-CMV retinitis antisense molecule (Vitravene trade mark, Isis Pharmaceuticals). "( Innovations in oligonucleotide drug delivery.
Lysik, MA; Wu-Pong, S, 2003
)
1.76
"Oligonucleotides are a very useful tool to control gene activity. "( Nuclear gene targeting using negatively charged liposomes.
Fahr, A; Neuhuber, W; Rascher, W; Repp, R; Schreier, H; Welz, C, 2000
)
1.75

Effects

Oligonucleotides (oligos) have been under clinical development for approximately the past 30 years. Oligon nucleotides have been ligated efficiently on solid-phase using CuAAC and SPAAC chemistry to produce up to 186-mer triazole linked DNA products. All oligonucleots investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6.

ExcerptReferenceRelevance
"Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases."( Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model.
An, HJ; Bae, S; Gu, H; Gwon, MG; Jung, HJ; Kim, YA; Lee, SJ; Leem, J; Park, KK, 2022
)
1.44
"Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning."( DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning.
Alieva, EE; Andreeva, OA; Oberemok, VV, 2023
)
2.19
"Oligonucleotides (oligos) have been under clinical development for approximately the past 30 years, beginning with antisense oligonucleotides (ASOs) and apatmers and followed about 15 years ago by siRNAs. "( FDA-Approved Oligonucleotide Therapies in 2017.
Castanotto, D; Stein, CA, 2017
)
1.9
"All oligonucleotides investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6 and colorectal cancer cell line HCT-116 p53-/-."( Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality.
Amato, T; Esposito, V; Galeone, A; Mayol, L; Russo, A; Russo, G; Virgilio, A, 2017
)
0.94
"Free oligonucleotides have been nearly inactive."( [Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus].
Bessudnova, EV; Chelobanov, BP; Levina, AS; Mazurkova, NA; Repkova, MN; Stetsenko, DA; Zarytova, VF,
)
0.8
"Oligonucleotides have been ligated efficiently on solid-phase using CuAAC and SPAAC chemistry to produce up to 186-mer triazole linked DNA products. "( Solid phase click ligation for the synthesis of very long oligonucleotides.
Brown, T; El-Sagheer, AH; Qiu, J, 2013
)
2.08
"Oligonucleotides have been gaining considerable attention as promising and effective candidate therapeutics against various diseases. "( Therapeutic oligonucleotides and delivery technologies: Research topics in Japan.
Murakami, M,
)
1.95
"Oligonucleotides (ONs) have shown great promise as therapeutic agents for various diseases. "( Microfluidic assembly of lipid-based oligonucleotide nanoparticles.
Huang, X; Lee, LJ; Lee, RJ; Wu, Y; Xue, W; Yu, B; Zhu, J, 2011
)
1.81
"The oligonucleotides have been examined as substrates for phosphodiester bond synthesis in the presence of ATP as catalysed by yeast ATP (CTP): tRNA nucleotidyltransferase."( Preparation of oligonucleotides corresponding to the acceptor stem of yeast tRNAPhe and their interaction with yeast ATP(CTP):tRNA nucleotidyltransferase.
Cramer, F; McLaughlin, LW; Sternbach, H; Wang, GH, 1984
)
1.1
"Oligonucleotides have been extensively studied for their potential as therapeutic agents. "( An experimental model for interpreting percutaneous penetration of oligonucleotides that incorporates the role of keratinocytes.
Brand, RM; Haase, K; Hannah, TL; Iversen, PL, 1998
)
1.98
"Oligonucleotides have been extensively studied as antisense or antigene agents that can potentially modulate the expression of specific genes. "( Antiproliferative activity of G-rich oligonucleotides correlates with protein binding.
Bates, PJ; Kahlon, JB; Miller, DM; Thomas, SD; Trent, JO, 1999
)
2.02
"Oligonucleotides have been coupled covalently to a pre-activated surface."( Changing functionality of surfaces by directed self-assembly using oligonucleotides--the Oligo-Tag.
Bier, FF; Ehrentreich-Förster, E; Kleinjung, F; Scheller, FW, 1999
)
1.26

Actions

ExcerptReferenceRelevance
"CpG oligonucleotides (CpG ODN) activate and support the maturation of immune cells, including plasmacytoid dendritic cells and B lymphocytes, that express Toll-like receptor 9 (TLR9) and are capable of presenting tumor antigens to T cells."( TLR-9 agonist immunostimulatory sequence adjuvants linked to cancer antigens.
Klinman, DM; Shirota, H, 2014
)
0.88

Toxicity

ExcerptReferenceRelevance
"Sulfur modification of oligodeoxynucleotides produces nuclease resistance but also leads to toxic effects when these compounds are administered in vivo."( End-capped antisense oligodeoxynucleotides effectively inhibit gene expression in vivo and offer a low-toxicity alternative to fully modified phosphorothioate oligodeoxynucleotides.
Hebb, MO; Robertson, HA, 1997
)
0.3
" DAC-30((R)) showed significant toxic effects on haEC and haSMC at each dose after > or =4 h and Lipofectin((R)) (LF) caused complete detachment of haEC and haSMC in medium containing 10% serum."( Toxicity, uptake kinetics and efficacy of new transfection reagents: increase of oligonucleotide uptake.
Axel, DI; Karsch, KR; Riessen, R; Runge, H; Spyridopoulos, I; Viebahn, R,
)
0.13
" Overall safety was evaluated by clinical adverse events, laboratory tests, and electrocardiograms."( Safety of intracoronary administration of c-myc antisense oligomers after percutaneous transluminal coronary angioplasty (PTCA).
Belardi, J; Fischman, DL; Grinfeld, L; Grossman, S; Long, R; Malcolm, A; Mon, G; Ormont, ML; Rodriguez, A; Roqué, F; Shi, Y; Zalewski, A; Zon, G, 2001
)
0.31
" As this oligonucleotide readily adopts an aggregate structure, a quadruplex, which may be associated with adverse physiologic effects, this study was performed using INX-3280 that had been converted to its monomeric form."( Toxicity and toxicokinetics of a phosphorothioate oligonucleotide against the c-myc oncogene in cynomolgus monkeys.
Blaquiere, M; Cremese, M; Devine, DV; Kornbrust, DJ; Kozlowska, H; Tortora, N; Webb, MS, 2001
)
0.31
" Additionally, preliminary results from experiments in SCID mice (mice with transplanted human immune cells) indicate that the human cells transduced with VRX496 and implanted into the SCID mice do not elicit any overt adverse effects."( Clinical protocol. A phase 1 open-label clinical trial of the safety and tolerability of single escalating doses of autologous CD4 T cells transduced with VRX496 in HIV-positive subjects.
MacGregor, RR, 2001
)
0.31
" These Ahr(nls) mice were found to be resistant to all 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxic responses that we examined, including hepatomegaly, thymic involution, and cleft palate formation."( Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor.
Bradfield, CA; Bunger, MK; Glover, E; Lahvis, GP; Lin, BC; Moran, SM; Thomae, TL, 2003
)
0.32
" Adverse events were collected during the first week and at 4 weeks after each injection."( Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults.
Dobson, S; Eiden, JJ; Gennevois, D; Halperin, SA; Langley, JM; Levitt, D; McCall-Sani, R; McNeil, S; Nest, GV; Smith, B, 2006
)
0.33
" Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups."( Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults.
Dobson, S; Eiden, JJ; Gennevois, D; Halperin, SA; Langley, JM; Levitt, D; McCall-Sani, R; McNeil, S; Nest, GV; Smith, B, 2006
)
0.33
" Other end points included other angiographic variables, adverse events through 30 days, and major adverse cardiac events."( Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial.
Alexander, JH; Califf, RM; Ferguson, TB; Gennevois, D; Gibson, M; Goyal, A; Hafley, G; Harrington, RA; Kouchoukos, NT; Lorenz, TJ; Mack, MJ; Peterson, ED, 2005
)
0.33
"66), on any secondary angiographic end point, or on the incidence of major adverse cardiac events at 1 year (101 [6."( Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial.
Alexander, JH; Califf, RM; Ferguson, TB; Gennevois, D; Gibson, M; Goyal, A; Hafley, G; Harrington, RA; Kouchoukos, NT; Lorenz, TJ; Mack, MJ; Peterson, ED, 2005
)
0.33
" Results can be achieved within 1 day and are less susceptible to possible toxic effects than phage generation or other methods that require DNA synthesis."( New method for evaluation of genotoxicity, based on the use of real-time PCR and lysogenic gram-positive and gram-negative bacteria.
Martín, R; Soberón, N; Suárez, JE, 2007
)
0.34
" The genotoxicity was less severe than the patulin, suggesting that citrinin is less toxic than patulin."( Evaluation of toxicity of the mycotoxin citrinin using yeast ORF DNA microarray and Oligo DNA microarray.
Hosoda, H; Ishizawa, YH; Iwahashi, H; Iwahashi, Y; Kitagawa, E; Kuboki, Y; Nobumasa, H; Suzuki, Y; Ueda, Y, 2007
)
0.34
" The most frequent adverse events were fatigue (55%), diarrhea (51%), nausea (44%), and hypertension (42%)."( Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.
Bass, MB; Benjamin, R; Chang, DD; Herbst, RS; Koutsoukos, A; Kurzrock, R; Mulay, M; Ng, C; Polverino, A; Purdom, M; Rosen, LS; Silverman, J; Sun, YN; Van Vugt, A; Wiezorek, JS; Xu, RY, 2007
)
0.34
"Active and safe reversibility of anticoagulation is an unmet need in clinical care."( A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor.
Alexander, JH; Becker, RC; Chan, MY; Harrington, RA; Rusconi, CP; Tonkens, RM, 2008
)
0.35
" There was no major bleeding and there were no other serious adverse events."( A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor.
Alexander, JH; Becker, RC; Chan, MY; Harrington, RA; Rusconi, CP; Tonkens, RM, 2008
)
0.35
" Sixteen patients (62%) experienced motesanib-related adverse events, most commonly lethargy (n=6), diarrhoea (n=4), fatigue (n=3), headache (n=3), and nausea (n=3)."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008
)
0.35
" The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%)."( Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
Bastholt, L; Daumerie, C; Droz, JP; Elisei, R; Eschenberg, MJ; Jarzab, B; Juan, T; Locati, LD; Martins, RG; Pacini, F; Schlumberger, MJ; Sherman, SI; Stepan, DE; Sun, YN; Wirth, LJ, 2009
)
0.35
" Direct administration of this AON in muscle of DM1 mouse models in vivo caused a significant reduction in the level of toxic (CUG)n RNA and a normalizing effect on aberrant premRNA splicing."( Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy.
Croes, HJ; de Kimpe, SJ; Furling, D; Gourdon, G; Mulders, SA; Platenburg, GJ; Thornton, CA; van den Broek, WJ; van Kuik-Romeijn, P; Wansink, DG; Wheeler, TM; Wieringa, B, 2009
)
0.35
" Safety was assessed with laboratory test results and by the incidence and severity of adverse events."( Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy.
Akdim, F; Baker, BF; Flaim, JD; Jukema, JW; Kastelein, JJ; Sijbrands, EJ; Stroes, ES; Su, J; Tribble, DL; Trip, MD; Wedel, MK; Yu, R, 2010
)
0.36
" Injection site reactions (mild to moderate erythema [90%]) and hepatic transaminase increases (17%) were the most common adverse events, leading to discontinuation in 2 subjects and 1 subject, respectively."( Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy.
Akdim, F; Baker, BF; Flaim, JD; Jukema, JW; Kastelein, JJ; Sijbrands, EJ; Stroes, ES; Su, J; Tribble, DL; Trip, MD; Wedel, MK; Yu, R, 2010
)
0.36
" The most common motesanib treatment-related grade 3 adverse events included hypertension (23%), fatigue (9%), and diarrhea (5%)."( Efficacy and safety of motesanib, an oral inhibitor of VEGF, PDGF, and Kit receptors, in patients with imatinib-resistant gastrointestinal stromal tumors.
Baker, L; Benjamin, RS; Blay, JY; Bui, BN; Duyster, J; Hartmann, JT; McCoy, S; Reichardt, P; Rosen, LS; Schöffski, P; Schuetze, S; Skubitz, K; Stepan, DE; Sun, YN; Van Oosterom, A, 2011
)
0.37
"Amyloid-beta peptide (Aβ) is shown to be toxic to the mitochondria and implicates this organelle in the pathogenesis of Alzheimer's disease."( Mortalin overexpression attenuates beta-amyloid-induced neurotoxicity in SH-SY5Y cells.
Chen, C; Qu, M; Wang, D; Xu, S; Yu, Z; Zhou, Z, 2011
)
0.37
" To better understand the function of IbsC and to decipher the sequence determinants for its toxic phenotype, we carried out extensive sequence analyses of the peptide."( Decoding toxicity: deducing the sequence requirements of IbsC, a type I toxin in Escherichia coli.
Li, Y; Mok, WW; Patel, NH, 2010
)
0.36
" Retene cardiotoxicity also differs mechanistically from the cardiac effects of non-alkylated phenanthrane, illustrating that alkyl groups can alter toxic action."( AhR2-mediated, CYP1A-independent cardiovascular toxicity in zebrafish (Danio rerio) embryos exposed to retene.
Hodson, PV; Incardona, JP; Pelkki, K; Scott, JA; Shepardson, S, 2011
)
0.37
" Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases."( Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia.
Frishman, W; Ricotta, DN,
)
0.13
" REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined."( A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.
Aberle, LH; Alexander, JH; Becker, RC; Bode, C; Buller, CE; Cohen, MG; Cornel, JH; Delarche, N; Kasprzak, JD; Mehran, R; Montalescot, G; Natarajan, M; Povsic, TJ; Ring, ME; Rynkiewicz, A; Vavalle, JP; Zelenkofske, SL; Zeymer, U, 2013
)
0.39
"At least 50% reversal is required to allow safe sheath removal after cardiac catheterization."( A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.
Aberle, LH; Alexander, JH; Becker, RC; Bode, C; Buller, CE; Cohen, MG; Cornel, JH; Delarche, N; Kasprzak, JD; Mehran, R; Montalescot, G; Natarajan, M; Povsic, TJ; Ring, ME; Rynkiewicz, A; Vavalle, JP; Zelenkofske, SL; Zeymer, U, 2013
)
0.39
" Safety assessments included adverse events, laboratory tests, and magnetic resonance imaging assessment of hepatic fat."( Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease.
Chin, W; Donovan, JM; Dufour, R; East, C; Gagne, C; Gaudet, D; McGowan, M; Stein, EA; Tribble, DL, 2012
)
0.38
"This document summarizes the current consensus opinion of the Exaggerated Pharmacology (EP) Subcommittee of the Oligonucleotide Safety Working Group on the appropriate strategies to assess potential adverse effects caused by an "exaggerated" degree of the intended pharmacologic activity of an oligonucleotide (ON)."( Oligo safety working group exaggerated pharmacology subcommittee consensus document.
Cavagnaro, J; Foy, J; Gamba-Vitalo, C; Guimond, A; Kornbrust, D; Levin, A; Pavco, P, 2013
)
0.39
" In the present study, we investigated hepatic transcription profiles of mice administered non-toxic and toxic LNA gapmers."( Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice.
Burdick, AD; Enayetallah, AE; Hollingshead, BD; Kakiuchi-Kiyota, S; Koza-Taylor, PH; Mantena, SR; Mathialagan, N; Nelms, LF; Reed, LA; Ryan, AM; Warneke, JA; Whiteley, LO, 2014
)
0.63
" Adverse events included injection site reactions and flu-like symptoms."( Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.
Chin, W; Duell, PB; East, C; Guyton, JR; Mittleman, RS; Moriarty, PM; Santos, RD, 2015
)
0.42
"Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects."( Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects.
Andersen, G; Boltje, I; Chin, W; Culm-Merdek, K; Hard, ML; Li, Z; Pabst, G; Singh, T; von Moltke, LL; Wagener, G, 2014
)
0.4
" The most common treatment-emergent adverse events (TEAEs) were diarrhea (74 %), nausea (51 %), fatigue (51 %), rash (51 %), and injection-site reactions (49 %)."( Antitumor activity and safety of combination therapy with the Toll-like receptor 9 agonist IMO-2055, erlotinib, and bevacizumab in advanced or metastatic non-small cell lung cancer patients who have progressed following chemotherapy.
Bexon, AS; Boyd, TE; Conkling, P; de La Bourdonnaye, G; Mita, AC; Nemunaitis, JJ; Richards, DA; Smith, DA; Wages, D, 2014
)
0.4
" Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain."( Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data.
Cicero, AF; Ertek, S; Tartagni, E, 2014
)
0.4
" Safety assessments included renal, hepatic, and haematological monitoring and recording of adverse events."( Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.
Campion, G; De Kimpe, SJ; Deconinck, N; Eagle, M; Guglieri, M; Hood, S; Kraus, JE; Liefaard, L; Lourbakos, A; Morgan, A; Muntoni, F; Nakielny, J; Quarcoo, N; Ricotti, V; Rolfe, K; Servais, L; Straub, V; Topaloglu, H; Voit, T; Wardell, C; Wilson, R; Wright, P, 2014
)
0.4
" The most common adverse events in drisapersen-treated patients were injection-site reactions (14 patients given continuous drisapersen, 15 patients given intermittent drisapersen, and six given placebo) and renal events (13 for continuous drisapersen, 12 for intermittent drisapersen, and seven for placebo), most of which were subclinical proteinuria."( Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.
Campion, G; De Kimpe, SJ; Deconinck, N; Eagle, M; Guglieri, M; Hood, S; Kraus, JE; Liefaard, L; Lourbakos, A; Morgan, A; Muntoni, F; Nakielny, J; Quarcoo, N; Ricotti, V; Rolfe, K; Servais, L; Straub, V; Topaloglu, H; Voit, T; Wardell, C; Wilson, R; Wright, P, 2014
)
0.4
" Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials."( Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients.
de Bruijne, J; Hodges, MR; Janssen, HL; Kupcova, V; Lawitz, EJ; Maan, R; Reesink, HW; Rodriguez-Torres, M; van der Meer, AJ; van der Ree, MH; van Vliet, A; Welzel, TM; Wiercinska-Drapalo, A; Zeuzem, S, 2014
)
0.4
" Remarkably, the mRNA transcripts commonly reduced by toxic LNA ASOs were generally not strongly associated with any particular biological process, cellular component or functional group."( Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.
Bennett, CF; Bui, HH; Burel, SA; Cauntay, P; Crooke, ST; Dan, A; Freier, SM; Hart, CE; Henry, SP; Hsiao, J; Hung, G; Katz, M; Machemer, T; Prakash, TP; Sabripour, M; Seth, PP; Swayze, EE; Watt, A; Younis, H, 2016
)
0.69
" For developing safe and effective gapmer drugs, a deeper understanding of the mechanisms of hepatotoxicity is required."( Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides.
Gahara, Y; Hori, S; Kasuya, T; Kugimiya, A; Nakajima, M; Rokushima, M; Watanabe, A; Yanagimoto, T, 2016
)
0.65
" Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria."( Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.
Buyse, G; Campion, G; de Kimpe, SJ; Goemans, NM; Kroksmark, AK; Lourbakos, A; Tulinius, M; van den Hauwe, M; van Deutekom, JC; Wilson, RJ, 2016
)
0.43
" Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time."( Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.
Mustonen, EK; Palomäki, T; Pasanen, M, 2017
)
0.46
" In healthy volunteers, AZD1419 was found to be safe and well-tolerated."( First-in-Human Study With the Inhaled TLR9 Oligonucleotide Agonist AZD1419 Results in Interferon Responses in the Lung, and Is Safe and Well-Tolerated.
Bell, J; Campbell, JD; Candia, AF; Coffman, RL; Delaney, S; Floettmann, S; Fuhr, R; Hessel, EM; Jackson, S; Keeling, D; Kell, S; Lum, J; McHale, M; Robinson, I; Traquina, P; Wong, C, 2018
)
0.48
" Specific detection of vaccine-related adverse events is resource-intensive, time-consuming, and difficult to achieve during an outbreak."( Development of a Real-Time Reverse Transcription-PCR Assay for Global Differentiation of Yellow Fever Virus Vaccine-Related Adverse Events from Natural Infections.
Hughes, HR; Kayiwa, J; Lambert, AJ; Lutwama, J; Mossel, EC; Russell, BJ, 2018
)
0.48
"Many patients with spinal muscular atrophy (SMA) who might benefit from intrathecal antisense oligonucleotide (nusinersen) therapy have scoliosis or spinal fusion that precludes safe drug delivery."( Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy.
Brigatti, KW; Carson, VJ; Fox, MD; Hendrickson, C; Mackenzie, W; Miller, F; Puffenberger, EG; Reed, RM; Robinson, DL; Strauss, KA; Young, M,
)
0.13
"Preliminary observations reveal the SIC to be relatively safe and well tolerated in SMA patients with advanced disease and spinal fusion."( Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy.
Brigatti, KW; Carson, VJ; Fox, MD; Hendrickson, C; Mackenzie, W; Miller, F; Puffenberger, EG; Reed, RM; Robinson, DL; Strauss, KA; Young, M,
)
0.13
"One of the key questions for nearly all oligonucleotide therapeutic programs is how to properly extrapolate no-observed adverse effect levels (NOAELs) identified in nonclinical (animal) toxicity studies to the human equivalent dose to enable selection of an appropriate safe starting dose level in normal subjects or patients."( Extrapolation of Oligonucleotide Dose Levels Used in Nonclinical Toxicity Studies to Selection of Safe Starting Dose Levels in Human Clinical Trials.
Kornbrust, D, 2019
)
0.51
"Single and multiple doses of inhaled eluforsen up to 50 mg were safe and well tolerated."( Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis.
Boff, M; Bouisset, F; Cipolli, M; De Boeck, K; den Hollander, W; Drevinek, P; Elborn, JS; Henig, N; Montgomery, S; Paquette-Lamontagne, N; Perquin, J; Pressler, T; Schwarz, C; Tomkinson, N, 2020
)
0.56
"Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients."( Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis.
Boff, M; Bouisset, F; Cipolli, M; De Boeck, K; den Hollander, W; Drevinek, P; Elborn, JS; Henig, N; Montgomery, S; Paquette-Lamontagne, N; Perquin, J; Pressler, T; Schwarz, C; Tomkinson, N, 2020
)
0.56
" Safety assessments included incidence of adverse events (AEs), physical and neurological examinations, vital signs, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and electrocardiograms."( An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials.
Bhan, I; Darras, BT; Farrar, MA; Farwell, W; Finkel, RS; Foster, R; Gheuens, S; Hughes, SG; Mercuri, E, 2019
)
0.51
" Eleven patients reported adverse events that were related to the study procedures, comprising back pain in seven patients and post-lumbar-puncture headache following intrathecal administration in four patients."( Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 - A Prospective Observational Study.
Greckl, E; Hiebeler, M; Kirschner, J; Lochmüller, H; Pechmann, A; Schoser, B; Stahl, K; Stauber, J; Thiele, S; Walter, MC; Wenninger, S, 2019
)
0.51
" Eight infants had adverse events considered possibly related to nusinersen by the study investigators."( Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.
Ben-Omran, T; Bertini, E; Bhan, I; Braley, G; Butterfield, RJ; Crawford, TO; De Vivo, DC; Farwell, W; Finkel, RS; Foster, R; Fradette, S; Gheuens, S; Hwu, WL; Johnson, K; Jong, YJ; Kerr, D; Kirschner, J; Kuntz, NL; Parsons, JA; Petrillo, M; Reyna, SP; Ryan, MM; Sandrock, AW; Sansone, VA; Shu, F; Staropoli, JF; Stebbins, C; Swoboda, KJ; Topaloglu, H, 2019
)
0.51
" The study's outcome measures were technical success, adverse events and radiation exposure."( Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.
Brountzos, E; Efstathopoulos, E; Filippiadis, D; Palaiodimou, L; Palialexis, K; Papadopoulou, M; Ploussi, A; Reppas, L; Spiliopoulos, S; Tsivgoulis, G; Zompola, C, 2020
)
0.56
" No adverse events were documented following the procedures."( Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.
Brountzos, E; Efstathopoulos, E; Filippiadis, D; Palaiodimou, L; Palialexis, K; Papadopoulou, M; Ploussi, A; Reppas, L; Spiliopoulos, S; Tsivgoulis, G; Zompola, C, 2020
)
0.56
"An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD)."( Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.
Clemens, PR; Connolly, AM; Harper, AD; Hoffman, EP; Mah, JK; McDonald, CM; Morgenroth, LP; Osaki, H; Rao, VK; Satou, Y; Smith, EC; Yamashita, T; Zaidman, CM, 2020
)
0.56
" Viltolarsen was well tolerated; no treatment-emergent adverse events required dose reduction, interruption, or discontinuation of the study drug."( Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.
Clemens, PR; Connolly, AM; Harper, AD; Hoffman, EP; Mah, JK; McDonald, CM; Morgenroth, LP; Osaki, H; Rao, VK; Satou, Y; Smith, EC; Yamashita, T; Zaidman, CM, 2020
)
0.56
" There were no nusinersen-related adverse events (AEs) and no study discontinuations due to nusinersen-related AEs."( Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study.
Acsadi, G; Castro, D; Crawford, TO; Farwell, W; Gambino, G; Müller-Felber, W; Natarajan, N; Ramirez-Schrempp, D; Richardson, R; Shieh, PB; Sun, P, 2021
)
0.62
" Treatment-related adverse events occurred in 21 patients (65."( A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Andritsos, L; Anyanwu, S; Bacon, L; Bouabdallah, R; Delafont, B; Dyer, MJS; Fayad, L; Hamid, O; Hayat, A; Hess, B; Jiang, Y; Kurzrock, R; Lee, ST; Martinez, P; Miah, K; Ribrag, V; Rizzieri, D, 2021
)
0.62
" One treatment-related serious adverse event (emesis leading to intubation) occurred during general anesthesia."( Laboratory monitoring of nusinersen safety.
Connolly, AM; Gibbons, JL; Goedeker, NL; Varadhachary, AS; Zaidman, CM, 2021
)
0.62
"Intrathecal nusinersen is generally safe and well-tolerated, including in patients requiring oral anxiolysis, general sedation, and fluoroscopic guidance."( Laboratory monitoring of nusinersen safety.
Connolly, AM; Gibbons, JL; Goedeker, NL; Varadhachary, AS; Zaidman, CM, 2021
)
0.62
" The most common adverse events were related to tolerability and included injection-site reactions (average of 24% of all volanesorsen injections vs 0·2% of placebo injections), which were all mild or moderate."( Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.
Alexander, VJ; Gaudet, D; Gouni-Berthold, I; Hegele, RA; Hughes, SG; Hurh, E; Moriarty, PM; O'Dea, LSL; Steinhagen-Thiessen, E; Stroes, ESG; Tsimikas, S; Witztum, JL; Yang, Q, 2021
)
0.62
" The highly toxic compounds showed the greatest amount of metabolites and a low degree of tissue accumulation."( Safety, Tissue Distribution, and Metabolism of LNA-Containing Antisense Oligonucleotides in Rats.
Braendli-Baiocco, A; Brink, A; Dzygiel, P; Festag, M; Fischer, G; Hetzel, U; Husser, C; Kipar, A; Koller, E; Lenz, B; Mihatsch, MJ; Romero-Palomo, F; Schadt, S; Sewing, S; Steinhuber, B; Tessier, Y; Winter, M, 2021
)
0.85
" Treatment-emergent adverse events (TEAEs) occurred in all casimersen- and placebo-treated participants and were mostly mild (over 91."( Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial.
East, L; Han, B; Koenig, E; Kuntz, NL; Shieh, PB; Upadhyay, S; Wagner, KR, 2021
)
0.62
" The most common adverse events were fatigue (44%), nausea (42%), diarrhea (40%), pyrexia (36%), anemia (32%), and vomiting (27%)."( Safety and Efficacy of a DNA Oligonucleotide Therapy in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Al-Katib, AM; Escobar, C; Harb, W; Jacobson, CA; Klencke, B; Lakhani, N; Maris, MB; McCaul, K; Patel, P; Patel-Donnelly, D; Westin, J, 2022
)
0.72
" Biogen safety database data up to June 30, 2019 were also included to capture adverse events (AEs) from after the interim analysis cutoff date."( Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database.
Hoshino, M; Makioka, H; Matsuda, N; Nakamura, G; Takasaki, S; Wataya, T, 2023
)
0.91
" Although ASO drugs are efficacious in treating some diseases that are untargetable by small-molecule chemical drugs, concerns on adverse drug reactions (ADRs) and toxicity cannot be ignored."( Adverse Drug Reactions and Toxicity of the Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.
Alhamadani, F; Bahal, R; Manautou, JE; Parikh, R; Rasmussen, TP; Wu, H; Zhang, K; Zhong, XB, 2022
)
0.72
" The only side effect was post lumbar puncture headache."( Longer-term follow-up of nusinersen efficacy and safety in adult patients with spinal muscular atrophy types 2 and 3.
Abraham, A; Abramovich, B; Ben-Shushan, S; Drory, VE; Fainmesser, Y; Lavon, A; Spector, L, 2022
)
0.72
" There have been no treatment-related serious adverse events and no discontinuations."( Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.
Clemens, PR; Connolly, AM; Harper, AD; Hoffman, EP; Mah, JK; McDonald, CM; Nakagawa, T; Rao, VK; Smith, EC; Zaidman, CM, 2022
)
0.72
" Except for 2 fatal cases, not related to the treatment, no serious adverse events were reported."( Safety, tolerability, and efficacy of a widely available nusinersen program for Polish children with Spinal Muscular Atrophy.
Biedroń, A; Boćkowski, L; Chmielewski, D; Cichosz, D; Czyżyk, E; Dudzińska, M; Gadowska, E; Jasiński, M; Kempisty, A; Kostera-Pruszczyk, A; Kotulska, K; Masztalerz, A; Mazurkiewicz-Bełdzińska, M; Młynarczyk, E; Pierzchlewicz, K; Pietruszewski, J; Przysło, Ł; Rabczenko, D; Steinborn, B; Tomaszek, K, 2022
)
0.72
" Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study."( Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update.
Aquino, P; Benson, MD; Berk, JL; Brannagan, TH; Coelho, T; Conceição, I; Drachman, B; Dyck, PJ; Gamez, J; Gentile, L; Gertz, M; Gorevic, P; Kristen, AV; Mazzeo, A; Merlini, G; Narayana, A; Obici, L; Olugemo, K; Plana, JMC; Plante-Bordeneuve, V; Polydefkis, MJ; Wang, AK; Whelan, C, 2022
)
0.72
"No serious adverse events or clinically relevant abnormalities in any laboratory parameters were noted."( Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects.
Hoenlinger, A; Hurh, E; Karwatowska-Prokopczuk, E; Lesogor, A; Margolskee, A; Tsimikas, S; Xia, S; Yan, JH,
)
0.13
" Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate."( Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study.
Clemens, PR; Connolly, AM; Harper, AD; Hoffman, EP; Mah, JK; McDonald, CM; Nakagawa, T; Rao, VK; Smith, EC; Zaidman, CM, 2023
)
0.91
" Common adverse events were injection site reactions and platelet count decrease, consistent with previous studies."( Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial.
Alexander, VJ; Arca, M; Gaudet, D; Gouni-Berthold, I; Jones, A; Jones, R; Soran, H; Stroes, ESG; Tsimikas, S; Watts, L; Witztum, JL; Xia, S,
)
0.13
" Allometric interspecies scaling allowed us to define the first-in-class LNA-i-miR-221 safe starting dose for the clinical translation."( Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.
Arbitrio, M; Barbieri, V; Bertucci, B; Brescia, A; Caracciolo, D; Ciliberto, D; Cordua, A; Cuomo, O; De Fina, MR; Di Francesco, AE; Di Martino, MT; Di Paola, ED; Fiorillo, L; Gualtieri, S; Lopreiato, M; Manti, F; Riillo, C; Salvino, A; Scionti, F; Staropoli, N; Tagliaferri, P; Tassone, P; Thunarf, F; Zito, MC, 2023
)
0.91

Pharmacokinetics

Oligonucleotides have a low systemic half-life and rapid degradation. Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligon nucleotides in vivo.

ExcerptReferenceRelevance
" An initial half-life of 15-25 min represents distribution out of the plasma compartment and a second half-life of 20-40 h represents elimination from the body."( In vivo studies with phosphorothioate oligonucleotides: pharmacokinetics prologue.
Iversen, P, 1991
)
0.55
" The purposes of this review are to place oligonucleotide therapeutics in the context of modern molecular drug discovery and to summarize progress in understanding the pharmacodynamic properties of oligonucleotides designed to bind to nucleic acid receptors."( Progress toward oligonucleotide therapeutics: pharmacodynamic properties.
Crooke, ST, 1993
)
0.47
" As an emerging technology, the results of only two pharmacokinetic investigations with 99mTc-labeled DNA have been reported thus far, both from this laboratory."( Pharmacokinetics of 99mTc-labeled oligonucleotides.
Hnatowich, DJ, 1996
)
0.57
"To characterize the pharmacokinetic and tissue distribution profiles of a nucleotide-based thrombin inhibitor (GS522, phosphodiester oligonucleotide, GGTTGGTGTGGTTGG) following intravenous administration to rats."( Pharmacokinetics and biodistribution of a nucleotide-based thrombin inhibitor in rats.
Reyderman, L; Stavchansky, S, 1998
)
0.3
"The pharmacokinetic and biodistribution profiles of GS522 following intravenous administration to rats at three doses were characterized."( Pharmacokinetics and biodistribution of a nucleotide-based thrombin inhibitor in rats.
Reyderman, L; Stavchansky, S, 1998
)
0.3
" Differences in pharmacokinetic properties between the antiviral monomers and the heterodimers were evaluated using liposomal formulations of 3H-labelled AZT heterodimers as model compounds."( In vitro anti-human immunodeficiency virus and anti-hepatitis B virus activities and pharmacokinetic properties of heterodinucleoside phosphates containing AZT or ddC.
Kuster, H; Peghini, PA; Schott, H; Schwendener, RA; Zahner, R, 1998
)
0.3
" To identify parameters that are important for the in vivo activity of aptamers acting on intravascular targets, we have studied binding characteristics in vitro, pharmacokinetic parameters in Sprague-Dawley rats, and inhibitory activity in a SCID mouse/human lymphocyte model of lymphocyte trafficking for both 2'F pyrimidine 2'OH purine RNA and ssDNA anti-human L-selectin aptamers."( Anti-L-selectin aptamers: binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo.
Chang, YF; O'Connell, D; Parma, DH; Ringquist, S; Watson, SR; Weigand, L, 2000
)
0.31
"A series of pharmacokinetic studies following systemic or local administration for the development of delivery systems for gene drugs, such as plasmid DNA and oligonucleotides, are reviewed."( Development of gene drug delivery systems based on pharmacokinetic studies.
Hashida, M; Nishikawa, M; Takakura, Y; Yamashita, F, 2001
)
0.51
" NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life."( Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.
Bendele, RA; Bolin, R; Drolet, DW; Farmer, JA; Gill, SC; Judkins, MB; Nelson, J; Nixon, K; Tucker, CE; Wolf, JL; Zack, PM, 2000
)
0.31
" These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials."( Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.
Bendele, RA; Bolin, R; Drolet, DW; Farmer, JA; Gill, SC; Judkins, MB; Nelson, J; Nixon, K; Tucker, CE; Wolf, JL; Zack, PM, 2000
)
0.31
" The current study analyzed the affinity of patient IgG for LJP 394 prior to and following 4 months of treatment with LJP 394 to determine if pretreatment affinity influenced pharmacodynamic response."( Pre-treatment affinity for LJP 394 influences pharmacodynamic response in lupus patients.
Aranow, C; Cash, JM; Cronin, ME; Furie, RA; Iverson, GM; Katz, RS; Linnik, MD; McNeeley, PA; Weisman, MH, 2001
)
0.31
" It has approximately 130 min of half-life of blood TFO."( Pharmacokinetics of (111)In-labeled triplex-forming oligonucleotide targeting human N-myc gene.
Cho, JG; Kim, MK; Oh, EJ; Park, GH; Park, MK; Sohn, J; Yoon, EJ, 2002
)
0.31
"The purpose of our study was to investigate the pharmacology of clofarabine and its triphosphate and the pharmacodynamic actions in circulating blasts obtained from acute leukemia patients who entered a Phase I clinical trial of clofarabine."( Pharmacokinetics and pharmacodynamics of plasma clofarabine and cellular clofarabine triphosphate in patients with acute leukemias.
Ayres, M; Bonate, P; Du, M; Faderl, S; Gandhi, V; Kantarjian, H; Keating, MJ; Plunkett, W; Rios, MB, 2003
)
0.32
" Cellular pharmacokinetic studies done at the end of the first clofarabine infusion in 26 patients appeared dose proportional but showed a wide variation in the concentrations of clofarabine triphosphate."( Pharmacokinetics and pharmacodynamics of plasma clofarabine and cellular clofarabine triphosphate in patients with acute leukemias.
Ayres, M; Bonate, P; Du, M; Faderl, S; Gandhi, V; Kantarjian, H; Keating, MJ; Plunkett, W; Rios, MB, 2003
)
0.32
" Noncompartmental pharmacokinetic analysis was performed using PK Solutions software."( Pharmacokinetics of intrathecal oligodeoxynucleotides.
Bernards, CM; Krupp, JL, 2004
)
0.32
"Mean residence time and terminal elimination half-life did not differ significantly among the three oligodeoxynucleotides at any sampling site."( Pharmacokinetics of intrathecal oligodeoxynucleotides.
Bernards, CM; Krupp, JL, 2004
)
0.32
" Method validation data are presented on three pharmacodynamic assays that will be utilised during this trial."( Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP.
Cummings, J; Dive, C; Durkin, J; LaCasse, E; Lefebvre, C; Ranson, M; St-Jean, M; Ward, TH, 2005
)
0.33
" For pharmacokinetic analyses, concentrations of aptamers in plasma and aqueous humor were determined over time following bilateral subconjunctival administration to Dutch-belted rabbits using a hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay."( Pharmacologic and pharmacokinetic assessment of anti-TGFbeta2 aptamers in rabbit plasma and aqueous humor.
Epstein, DM; Gilbert, M; Kurz, JC; Lewis, SD; Marsh, HN; McCauley, TG; Merlino, PG, 2006
)
0.33
"Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays."( Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP.
Cummings, J; Dive, C; Durkin, J; Ganganagari, JR; Jayson, G; Lacasse, E; Ranson, M; St-Jean, M, 2006
)
0.33
" The primary objective was to determine the safety profile and to characterize the pharmacodynamic responses in this first-in-human study."( First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Aberle, LG; Alexander, JH; Becker, RC; Cannon, RO; Dyke, CK; Harrington, RA; Kleiman, NS; Lin, M; Melloni, C; Myles, SK; Rusconi, CP; Steinhubl, SR, 2006
)
0.33
" Pharmacodynamic samples were collected serially."( First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Aberle, LG; Alexander, JH; Becker, RC; Cannon, RO; Dyke, CK; Harrington, RA; Kleiman, NS; Lin, M; Melloni, C; Myles, SK; Rusconi, CP; Steinhubl, SR, 2006
)
0.33
"To test the multiple repeat-dose safety, intraindividual pharmacodynamic reproducibility and graded active reversibility of REG1."( A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor.
Alexander, JH; Becker, RC; Chan, MY; Harrington, RA; Rusconi, CP; Tonkens, RM, 2008
)
0.35
"This is the first human study demonstrating multiple repeat-dose safety, intraindividual pharmacodynamic reproducibility and graded active reversibility of an RNA aptamer-oligonucleotide antidote pair."( A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor.
Alexander, JH; Becker, RC; Chan, MY; Harrington, RA; Rusconi, CP; Tonkens, RM, 2008
)
0.35
" Patients were randomized to receive a single oral dose of ketoconazole 400 mg either on day 8 (Sequence 1; n = 7) or day 15 (Sequence 2; n = 7), while pharmacokinetic samples were collected."( Effect of coadministration of ketoconazole, a strong CYP3A4 inhibitor, on pharmacokinetics and tolerability of motesanib diphosphate (AMG 706) in patients with advanced solid tumors.
Chen, L; Heath, EI; Ingram, M; Lorusso, P; Malburg, L; McGreivy, J; Melara, R; Pilat, MJ; Sun, YN; Wiezorek, J; Yan, L, 2008
)
0.35
" In conclusion, treatment with motesanib plus gemcitabine was well tolerated, with adverse event and pharmacokinetic profiles similar to that observed in monotherapy studies."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008
)
0.35
" The aim of this study was to characterize the pharmacokinetic interactions of mipomersen sodium with simvastatin and ezetimibe."( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe.
Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009
)
0.35
" Mipomersen sodium pharmacokinetic profiles were assessed following the first dose (mipomersen sodium alone) and the last dose (mipomersen sodium in combination with simvastatin or ezetimibe)."( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe.
Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009
)
0.35
"The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC(24)), maximum plasma concentration and apparent elimination half-life values of mipomersen sodium were similar when administered alone and in combination with oral simvastatin or oral ezetimibe."( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe.
Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009
)
0.35
"These data provide evidence that mipomersen sodium exhibits no clinically relevant pharmacokinetic interactions with the disposition and clearance of simvastatin or ezetimibe, and vice versa."( Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2'-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe.
Flaim, JD; Geary, RS; Riley, GC; Tribble, DL; vanVliet, AA; Wedel, MK; Yu, RZ, 2009
)
0.35
" Motesanib concentrations were fitted to a 2-compartment population pharmacokinetic model."( Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.
Bruno, R; Claret, L; Kuchimanchi, M; Lu, JF; Melara, R; Sun, YN; Sutjandra, L, 2010
)
0.36
"We performed detailed pharmacokinetic and pharmacodynamic modeling of REG1, an anticoagulation system composed of the direct factor IXa (FIXa) inhibitor pegnivacogin (RB006) and its matched active control agent anivamersen (RB007), with a focus on level of target inhibition to translate phase 1 results to phase 2 dose selection."( Dose selection for a direct and selective factor IXa inhibitor and its complementary reversal agent: translating pharmacokinetic and pharmacodynamic properties of the REG1 system to clinical trial design.
Alexander, JH; Becker, RC; Chan, MY; Cohen, MG; Harrington, RA; Povsic, TJ; Rusconi, CP; Wargin, WA; Zelenkofske, SL, 2011
)
0.37
" The human pharmacokinetic parameters were predicted using 1, 2, or at least 3 animal species."( Pharmacokinetic allometric scaling of oligonucleotides.
Mahmood, I, 2011
)
0.64
"Mipomersen was absorbed rapidly after SC administration; median tmax varied between 2 and 3 hours."( Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects.
Andersen, G; Boltje, I; Chin, W; Culm-Merdek, K; Hard, ML; Li, Z; Pabst, G; Singh, T; von Moltke, LL; Wagener, G, 2014
)
0.4
" The pharmacokinetic (PK) properties of mipomersen are generally consistent across all species studied, including mouse, rat, monkey, and humans."( Clinical and preclinical pharmacokinetics and pharmacodynamics of mipomersen (kynamro(®)): a second-generation antisense oligonucleotide inhibitor of apolipoprotein B.
Baker, BF; Crooke, ST; Geary, RS, 2015
)
0.42
" Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligonucleotides in vivo."( Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay.
Biscans, A; Coles, AH; Echeverria, D; Gilbert, JW; Godinho, BMDC; Haraszti, RA; Hassler, M; Khvorova, A; Nikan, M; Roux, L, 2017
)
0.9
"A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA)."( A Semi-Mechanistic Population Pharmacokinetic Model of Nusinersen: An Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy.
Biliouris, K; Fey, R; Gaitonde, P; Henry, S; Lesko, LJ; Nestorov, I; Norris, DA; Rogge, M; Schmidt, S; Trame, MN; Wang, Y; Yin, W, 2018
)
0.48
" The model-based simulation suggested that steady state weekly AUC and Cmax were very similar between 3 mg/kg and 200 mg flat dosing (geometric mean of AUC: 62."( Population pharmacokinetic analysis of danvatirsen supporting flat dosing switch.
Al-Huniti, N; Arfvidsson, C; Cook, C; Lyne, P; Mugundu, G; Pease, E; Scott, ML; Tong, X; Xu, H; Zhou, D, 2019
)
0.51
" This commentary, and the special issue as a whole, aims to highlight these emerging modalities and the efforts underway to better understand their unique pharmacokinetic and absorption, disposition, metabolism, and excretion (ADME) properties."( Pharmacokinetic and Drug Metabolism Properties of Novel Therapeutic Modalities.
Foti, RS; Rock, BM, 2019
)
0.51
"We describe tactics to assess pharmacokinetic (PK) and pharmacodynamic (PD) parameters of oligonucleotides."( ADME: Assessing Pharmacokinetic-Pharmacodynamic Parameters of Oligonucleotides.
Ahlström, C; Gennemark, P; Jansson-Löfmark, R, 2019
)
0.98
"Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool with many demonstrated applications in various phases of drug development and regulatory review."( Physiologically based pharmacokinetic (PBPK) modeling of RNAi therapeutics: Opportunities and challenges.
Fairman, K; Li, M; Lumen, A; Ning, B, 2021
)
0.62
" This population pharmacokinetic model was developed to clarify how to maintain targeted nusinersen exposure after an unforeseen one-time delay or missed dose."( Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Berger, Z; East, L; Farrar, MA; Farwell, W; Finkel, RS; Kirschner, J; MacCannell, D; Mercuri, E; Muntoni, F; Nestorov, I; Peng, J; Zhou, J, 2021
)
0.62
" All pharmacokinetic parameters were similar at weeks 7 and 60."( Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial.
East, L; Han, B; Koenig, E; Kuntz, NL; Shieh, PB; Upadhyay, S; Wagner, KR, 2021
)
0.62
" Using labeled sEVs administered to conscious rats, we developed a multiple compartment pharmacokinetic model to identify potential differences in the disposition of sEVs from three different cell types."( Novel Quantification of Extracellular Vesicles with Unaltered Surface Membranes Using an Internalized Oligonucleotide Tracer and Applied Pharmacokinetic Multiple Compartment Modeling.
Benson, EA; De Luca, T; Edwards, ME; Ferreira, CR; Stratford, RE, 2021
)
0.62
"Our method relies upon established laboratory techniques, can be tailored to a variety of biological questions regarding the pharmacokinetic disposition of extracellular vesicles, and will provide a complementary approach for the of study EV ligand-receptor interactions in the context of EV uptake and targeted therapeutics."( Novel Quantification of Extracellular Vesicles with Unaltered Surface Membranes Using an Internalized Oligonucleotide Tracer and Applied Pharmacokinetic Multiple Compartment Modeling.
Benson, EA; De Luca, T; Edwards, ME; Ferreira, CR; Stratford, RE, 2021
)
0.62
"Population pharmacokinetic models using integrated pharmacokinetic data from ten nusinersen clinical trials that included a broad range of participants with spinal muscular atrophy treated with intrathecal nusinersen were used to investigate different durations of treatment interruptions during maintenance treatment."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
"Our pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
" Therapeutics such as oligonucleotides, peptides and other biologicals suffer from low systemic half-life and rapid degradation."( Albumin-hitchhiking: Fostering the pharmacokinetics and anticancer therapeutics.
Ahmed, T; Famta, P; Jain, N; Murthy, A; Shah, S; Shahrukh, S; Singh, SB; Srinivasarao, DA; Srivastava, S; Vambhurkar, G, 2023
)
1.22
" Using pooled data from two phase I studies of participants with elevated triglycerides (Western: n = 48 and Japanese: n = 12), and two phase II studies of patients with hypertriglyceridemia, diabetes, and nonalcoholic fatty liver disease (n = 105), and statin-treated patients with dyslipidemia (n = 286), we developed population pharmacokinetic (PK) and PK/pharmacodynamic (PK/PD) models."( A population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis of vupanorsen from phase I and phase II studies.
Ahn, JE; Liu, J; Terra, SG, 2023
)
0.91
" Nonlinear mixed-effect population pharmacokinetic (PopPK) modeling was conducted to characterize the CSF and plasma pharmacokinetics (PK) of tominersen, and to identify and quantify the covariates that affect tominersen PKs."( Development of a population pharmacokinetic model to characterize the pharmacokinetics of intrathecally administered tominersen in cerebrospinal fluid and plasma.
Björnsson, M; Grimsey, P; Massonnet, B; Norris, DA; Portron, A; Sanwald Ducray, P; Silber Baumann, HE; Smart, K; Vatakuti, S; Yamamoto, Y, 2023
)
0.91

Compound-Compound Interactions

We investigated the effect of Bcl-2 small interfering RNA (siRNA) combined with miR-15a oligonucleotides (ODN) on the growth of Raji cells. We have compared conventional RFLP methods with PCR used in combination with allele specific oligon nucleotides. The results were used to diagnose AAT deficiency of the ZZ type.

ExcerptReferenceRelevance
" We have compared conventional RFLP methods with PCR used in combination with allele specific oligonucleotides or RFLP analysis, in a case of prenatal diagnosis of AAT deficiency of the ZZ type."( Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction (PCR). Comparison of conventional RFLP methods with PCR used in combination with allele specific oligonucleotides or RFLP analysis.
Gregersen, N; Hinkel, K; Newton, CR; Petersen, KB; Schwartz, M, 1989
)
0.69
" We have explored the possibility of using EDITH in combination with fast deprotection chemistry(e."( Evaluation of 3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) as a new sulfurizing reagent in combination with labile exocyclic amino protecting groups for solid-phase oligonucleotide synthesis.
Dignam, JC; Fong, GW; George, ST; Gray, SH; Jacob-Samuel, B; Li, L; Ma, MY, 1997
)
0.3
" A mutational analysis of nuclear protein binding in electrophoretic mobility shift assays in combination with specific antisera showed that in the CRE of the rat insulin I gene the imperfect CRE octamer-like sequence TGACGTCC interacts weakly with CREB and overlaps with two sequence motifs (TTGTTGAC and CCAAT) that bind winged helix-like proteins and the transcription factor NF-Y, respectively."( Gene-specific transcriptional activity of the insulin cAMP-responsive element is conferred by NF-Y in combination with cAMP response element-binding protein.
Blume, R; Eggers, A; Knepel, W; Siemann, G, 1998
)
0.3
" We have recently shown that a mixed backbone oligonucleotide targeting RIalpha can cooperatively inhibit human cancer cell growth when combined with selected cytotoxic drugs."( Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth.
Agrawal, S; Bianco, AR; Caputo, R; Ciardiello, F; Mendelsohn, J; Pepe, S; Pomatico, G; Tortora, G, 1999
)
0.3
", Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV)."( Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer.
Dorr, FA; Geary, RS; Holmlund, JT; Kindler, HL; Kunkel, K; Mani, S; Ratain, MJ; Rudin, CM, 2002
)
0.31
" We have examined the effect of this CDO alone and in combination with a range of common chemotherapeutic agents in colorectal cancer cell lines."( The in vitro effects of CRE-decoy oligonucleotides in combination with conventional chemotherapy in colorectal cancer cell lines.
Liu, WM; Propper, DJ; Scott, KA; Shahin, S, 2004
)
0.6
"LY900003 can be administered safely in combination with cisplatin and gemcitabine and is associated with antitumor activity in patients with advanced NSCLC."( A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer.
Belt, R; Dow, E; Figueroa, JA; Geary, R; George, S; Holmlund, J; Leonardo, J; McCachren, S; Miller, GL; Modiano, M; Oliver, JW; Otterson, GA; Ritch, P; Valdivieso, M; Villalona-Calero, MA, 2004
)
0.32
" Furthermore, the efficacy of immunotherapy combined with either 5-fluorouracil or irinotecan was similar to that of immunotherapy alone."( Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer.
Beck, S; Bourquin, C; Endres, S; Hartmann, G; Schreiber, S, 2006
)
0.6
" Preclinical studies have demonstrated synergistic antitumor activity when GEM231 is combined with docetaxel."( A phase I safety and dose escalation trial of docetaxel combined with GEM231, a second generation antisense oligonucleotide targeting protein kinase A R1alpha in patients with advanced solid cancers.
Desai, K; Einstein, M; Fields, A; Goel, S; Goldberg, G; Macapinlac, M; Mani, S; Martin, R; Volterra, F; Wadler, S; Wong, B, 2006
)
0.33
" Here, we evaluated the performances of this MIRU-VNTR typing system in combination with spoligotyping for the detection of transmission chains in a population-based study comprising 91% of culture-confirmed tuberculosis patients reported in 2003 in Hamburg, Germany."( Assessment of an optimized mycobacterial interspersed repetitive- unit-variable-number tandem-repeat typing system combined with spoligotyping for population-based molecular epidemiology studies of tuberculosis.
Diel, R; Haas, W; Locht, C; Niemann, S; Oelemann, MC; Rüsch-Gerdes, S; Supply, P; Vatin, V, 2007
)
0.34
" We examined the effects of two types of TLR9 agonists: a traditional CpG oligonucleotide and a novel immunomodulatory oligonucleotide in models of colon cancer, both alone and in combination with conventional cancer therapies."( Experimental therapy for colon cancer: anti-cancer effects of TLR9 agonism, combination with other therapeutic modalities, and dependence upon p53.
Rayburn, ER; Wang, H; Wang, W; Zhang, R, 2007
)
0.34
" In this study, the strategy of a semi-rational design of directed evolution combined with whole sequence and sites was developed."( A semi-rational design strategy of directed evolution combined with chemical synthesis of DNA sequences.
Cai, B; Gao, F; Liu, JG; Peng, RH; Xiong, AS; Xu, F; Yao, QH; Zhuang, J, 2007
)
0.34
"The aim of this open-label phase 1b study was to assess the safety and pharmacokinetics of motesanib in combination with gemcitabine in patients with advanced solid tumours."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008
)
0.35
" We report on a phase I/II trial of the XIAP antisense oligonucleotide AEG35156 in combination with reinduction chemotherapy."( Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
Altman, JK; Andreeff, M; Borthakur, G; Brandwein, J; Carter, BZ; Estey, EH; Hedley, DW; Jacob, C; Jolivet, J; Karp, JE; Kassis, J; LaCasse, E; Mak, DH; Morris, SJ; Schiller, GJ; Schimmer, AD; Tallman, MS; Xu, W, 2009
)
0.35
"Twenty-four patients with rapidly relapsed or refractory AML were treated with escalating doses of AEG35156 (12 to 250 mg/m(2)) as an intravenous solution over 2 hours and 32 patients were treated with the highest planned dose of 350 mg/m(2) in combination with idarubicin and high-dose cytarabine reinduction chemotherapy."( Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
Altman, JK; Andreeff, M; Borthakur, G; Brandwein, J; Carter, BZ; Estey, EH; Hedley, DW; Jacob, C; Jolivet, J; Karp, JE; Kassis, J; LaCasse, E; Mak, DH; Morris, SJ; Schiller, GJ; Schimmer, AD; Tallman, MS; Xu, W, 2009
)
0.35
" Among the patients receiving 350 mg/m(2) of AEG35156 in combination with chemotherapy, 10 (91%) of 11 who were refractory to a single induction chemotherapy regimen achieved CR/CRp after reinduction with AEG35156 and chemotherapy."( Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
Altman, JK; Andreeff, M; Borthakur, G; Brandwein, J; Carter, BZ; Estey, EH; Hedley, DW; Jacob, C; Jolivet, J; Karp, JE; Kassis, J; LaCasse, E; Mak, DH; Morris, SJ; Schiller, GJ; Schimmer, AD; Tallman, MS; Xu, W, 2009
)
0.35
"At the highest dose tested, AEG35156 knocks down its target and appears very effective when combined with chemotherapy in patients with AML refractory to a single induction regimen."( Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
Altman, JK; Andreeff, M; Borthakur, G; Brandwein, J; Carter, BZ; Estey, EH; Hedley, DW; Jacob, C; Jolivet, J; Karp, JE; Kassis, J; LaCasse, E; Mak, DH; Morris, SJ; Schiller, GJ; Schimmer, AD; Tallman, MS; Xu, W, 2009
)
0.35
"Treatment with motesanib was tolerable when combined with carboplatin/paclitaxel and/or panitumumab, with little effect on motesanib pharmacokinetics at the 125-mg once daily dose level."( Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer.
Blumenschein, GR; Gladish, G; McGreivy, J; O'Rourke, T; Parson, M; Reckamp, K; Sandler, A; Stephenson, GJ; Sun, YN; Ye, Y, 2010
)
0.36
"This phase Ib study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 102, a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in combination with bevacizumab or motesanib in patients with advanced solid tumors."( A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.
Anderson, A; Beaupre, DM; Deng, H; Leitch, IM; Oliner, KS; Park, DJ; Rosen, PJ; Shubhakar, P; Sweeney, CJ; Yee, LK; Zhu, M, 2010
)
0.36
"AMG 102 in combination with bevacizumab was well tolerated."( A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.
Anderson, A; Beaupre, DM; Deng, H; Leitch, IM; Oliner, KS; Park, DJ; Rosen, PJ; Shubhakar, P; Sweeney, CJ; Yee, LK; Zhu, M, 2010
)
0.36
"This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011
)
0.37
"Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6)."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011
)
0.37
" The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011
)
0.37
" Motesanib 125 mg QD was tolerable only in combination with erlotinib alone."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011
)
0.37
" The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR."( Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia.
Cook, H; Datto, M; Daugherty, FJ; Davis, PH; DeCastro, CM; Diehl, LF; Friedman, DR; Gockerman, JP; Lanasa, MC; Li, Z; Matta, KM; Moore, JO; Rehder, C; Rizzieri, D; Weinberg, JB, 2012
)
0.38
" We investigated the antitumor activity of motesanib, a selective antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit, alone and combined with chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI-H1299, and NCI-H1650) containing diverse genetic mutations."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012
)
0.38
" When combined with cisplatin, motesanib significantly inhibited the growth of Calu-6, NCI-H358, and NCI-H1650 tumor xenografts compared with either single agent alone (P < 0."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012
)
0.38
"These data demonstrate that motesanib had antitumor activity against five different human NSCLC xenograft models containing diverse genetic mutations, and that it had enhanced activity when combined with cisplatin or docetaxel."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012
)
0.38
" Here, we investigated the effect of Bcl-2 small interfering RNA (siRNA) combined with miR-15a oligonucleotides (ODN) on the growth of Raji cells."( The effect of Bcl-2 siRNA combined with miR-15a oligonucleotides on the growth of Raji cells.
Chen, S; Gao, Y; He, D; Hu, X; Li, W; Liu, G; Wu, H; Zhang, Y, 2013
)
0.86
"This Phase Ib trial assessed the maximum tolerated dose (MTD) and safety of the Toll-like receptor 9 agonist IMO-2055 combined with 5-fluorouracil, cisplatin, and cetuximab (PFE) as first-line palliative treatment in patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)."( Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
Brümmendorf, TH; Delord, JP; Forssmann, U; Goddemeier, T; Kaminsky, MC; Keller, U; Machiels, JP, 2013
)
0.39
" LY2181308 was administered with a loading dosage of three consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg."( Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML).
Andre, V; Andreeff, M; Brandt, JT; Callies, S; Erba, HP; Juckett, M; Kadam, S; Lahn, M; Sayar, H; Schmidt, S; Van Bockstaele, D, 2013
)
0.39
" EZN-3042 was administered as a single agent on days -5 and -2 and then in combination with a 4-drug reinduction platform on days 8, 15, 22, and 29."( A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA) antagonist, administered in combination with chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leu
Bhojwani, D; Bostrom, BC; Brown, P; Buchbinder, A; Carroll, WL; Cassar, J; Eckroth, E; Gaynon, P; Malvar, J; Morrison, D; Raetz, EA; Romanos-Sirakis, E; Sposto, R, 2014
)
0.4
" This open-label, single-sequence 2-period phase 1 study in healthy subjects evaluated the potential drug-drug interactions between mipomersen and warfarin."( Lack of clinical pharmacodynamic and pharmacokinetic drug-drug interactions between warfarin and the antisense oligonucleotide mipomersen.
Boltje, I; Grundy, JS; Hard, ML; Li, Z; Singh, T; von Moltke, LL, 2014
)
0.4
"EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy."( Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Bexon, A; Csoszi, T; Erfan, J; Evans, M; Fayette, J; Forssmann, U; Goddemeier, T; Hideghety, K; Holeckova, P; Klimak, P; Lee, LW; Nutting, C; Rottey, S; Ruzsa, A; Sen, M, 2014
)
0.4
"Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone."( Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).
Cheung, FY; Chiang, CL; Chong, M; Jolivet, J; Kwok, C; Kwong, P; Lai, M; Lee, C; Lee, FA; Leung, KC; Siu, SW; Tung, S; Zee, BC, 2016
)
0.43
"AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated."( Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).
Cheung, FY; Chiang, CL; Chong, M; Jolivet, J; Kwok, C; Kwong, P; Lai, M; Lee, C; Lee, FA; Leung, KC; Siu, SW; Tung, S; Zee, BC, 2016
)
0.43
" To assess the clinical significance of anti-SLA/LP Abs alone or in combination with anti-Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti-SLA/LP status."( Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis.
Bogdanos, DP; Dalekos, GN; Gampeta, S; Gatselis, NK; Goulis, J; Manoussakis, MN; Oikonomou, K; Renaudineau, Y; Zachou, K, 2015
)
0.42
" Moreover, imetelstat alone and in combination with trastuzumab reduced the CSC fraction and inhibited CSC functional ability, as shown by decreased mammosphere counts and invasive potential."( The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2+ breast cancer cells.
Herbert, BS; Koziel, JE, 2015
)
0.42
"In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29)."( Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.
Altun, A; Ataseven, H; Kaya, TT; Koyluoglu, G; Turgut, NH, 2016
)
0.43
" An additive antiproliferative effect was observed in combination with irinotecan."( Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer.
Abdullah, S; Abi-Jaoudeh, N; Anderson, V; Duffy, AG; Figg, WD; Fioravanti, S; Greten, TF; Lee, S; Levy, E; MacLeod, AR; Makarova-Rusher, OV; Peer, CJ; Raffeld, M; Rahma, OE; Revenko, AS; Steinberg, SM; Tomita, Y; Trepel, JB; Ulahannan, SV; Walker, M; Wood, BJ, 2016
)
0.43
"To assess whether immunostimulatory cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) combined with interleukin-2 (IL-2) improves the number of mitotic metaphases and the detection rate of chromosomal abnormalities in chronic lymphocytic leukaemia (CLL)."( Immunostimulation by cytosine-phosphate-guanine oligodeoxynucleotides in combination with IL-2 can improve the success rate of karyotype analysis in chronic lymphocytic leukaemia.
Chen, J; Huang, H; Lin, X, 2016
)
0.43
" FISH combined with CpG-ODN DSP30 plus IL-2 improved the detection rate of chromosomal abnormalities in CLL to 83."( Immunostimulation by cytosine-phosphate-guanine oligodeoxynucleotides in combination with IL-2 can improve the success rate of karyotype analysis in chronic lymphocytic leukaemia.
Chen, J; Huang, H; Lin, X, 2016
)
0.43
"CpG-ODN DSP30 combined with IL-2 is effective in improving the detection rate of chromosomal abnormalities in CLL cells."( Immunostimulation by cytosine-phosphate-guanine oligodeoxynucleotides in combination with IL-2 can improve the success rate of karyotype analysis in chronic lymphocytic leukaemia.
Chen, J; Huang, H; Lin, X, 2016
)
0.43
"We evaluated MK-4621, an oligonucleotide that binds and activates retinoic acid-inducible gene I (RIG-I), as monotherapy (NCT03065023) and in combination with the anti-programmed death 1 antibody pembrolizumab (NCT03739138)."( Treatment with a retinoic acid-inducible gene I (RIG-I) agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: results from two phase 1 studies.
Barlesi, F; Calvo, E; Chartash, E; Connors, EC; Dobrenkov, K; Gaudy-Marqueste, C; Italiano, A; Marabelle, A; Middleton, MR; Moreno, V; Romano, E; Wermke, M; Zhang, Y; Zhou, H, 2022
)
0.72
"8 mg) was administered intratumorally as a stable formulation with jetPEI™ twice weekly over a 4-week cycle as monotherapy and weekly in 3-week cycles for up to 6 cycles in combination with 200 mg pembrolizumab every 3 weeks for up to 35 cycles."( Treatment with a retinoic acid-inducible gene I (RIG-I) agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: results from two phase 1 studies.
Barlesi, F; Calvo, E; Chartash, E; Connors, EC; Dobrenkov, K; Gaudy-Marqueste, C; Italiano, A; Marabelle, A; Middleton, MR; Moreno, V; Romano, E; Wermke, M; Zhang, Y; Zhou, H, 2022
)
0.72
"Patients treated with MK-4621 monotherapy or in combination with pembrolizumab experienced tolerable safety and modest antitumor activity, and there was evidence that MK-4621 activated the RIG-I pathway."( Treatment with a retinoic acid-inducible gene I (RIG-I) agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: results from two phase 1 studies.
Barlesi, F; Calvo, E; Chartash, E; Connors, EC; Dobrenkov, K; Gaudy-Marqueste, C; Italiano, A; Marabelle, A; Middleton, MR; Moreno, V; Romano, E; Wermke, M; Zhang, Y; Zhou, H, 2022
)
0.72
" Herein, we developed a DNA hydrogel film combined with capillary self-driven action for the specific detection of the tumor marker EpCAM and further introduced Exo I for signal amplification."( Exo I signal amplification of a DNA hydrogel film combined with capillary self-driven action for EpCAM detection.
Bian, Y; Chen, L; Li, S; Lin, X; Wang, Z, 2023
)
0.91
" In this system, with the assistance of an auxiliary probe, the target miRNA-21 can be specifically combined with three-stranded probes to initiate the SDR reaction."( Development of a separation platform comprising magnetic beads combined with the CRISPR/Cas12a system enabling ultrasensitive and rapid detection of miRNA-21.
Li, H; Wang, S; Xu, J; Yu, R; Zhang, X; Zhao, W, 2023
)
0.91

Bioavailability

ExcerptReferenceRelevance
" This is the first bioavailability study on a short nonionic oligonucleotide analogue, a class of molecules with potential biomedical applications."( Synthesis and biodistribution of a short nonionic oligonucleotide analogue in mouse with a potential to mimic peptides.
Benner, SA; Boelsterli, UA; Boess, F; Eschgfäller, B; König, M, 1998
)
0.3
"The chemical modification of antisense oligodeoxynucleotides (ODNs) by conjugating synthetic peptides of known membranotropic activities to the 3' and/or 5' terminus of ODNs may serve two functions that are important for increasing their bioavailability by protecting the ODNs from exonuclease digestion and facilitated delivery into cells."( Use of Nalpha-Fmoc-cysteine(S-thiobutyl) derivatized oligodeoxynucleotides for the preparation of oligodeoxynucleotide-peptide hybrid molecules.
Haralambidis, J; Soukchareun, S; Tregear, G,
)
0.13
" In the present study, we have used HYB 165, a novel DNA/RNA hybrid mixed backbone oligonucleotide that exhibits improved pharmacokinetic and bioavailability properties in vivo and is presently undergoing Phase I trials."( Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth.
Agrawal, S; Bianco, AR; Caputo, R; Ciardiello, F; Mendelsohn, J; Pepe, S; Pomatico, G; Tortora, G, 1999
)
0.3
"Bioactivatable protecting groups represent an enormously powerful tool to increase bioavailability or to generally help deliver drugs to cells."( Prodrugs of biologically active phosphate esters.
Schultz, C, 2003
)
0.32
" The Fujita-Ban variant of the classical Free-Wilson analysis gave a highly significant correlation for a series of 48 relatively small molecules demonstrating that (i) the partial contributions of substituents to biological activity (EC(50)) are additive and (ii) assuming similar bioavailability for all quinolines studied, the larger molecules cannot be accommodated within a still unknown biological receptor."( Synthesis and activity of substituted 2-phenylquinolin-4-amines, antagonists of immunostimulatory CpG-oligodeoxynucleotides.
Bojarski, AJ; Henary, M; Macfarlane, DE; Manzel, L; Ruiz, P; Say, M; Strekowski, L, 2003
)
0.32
" Optimization of the sequence, length, and bioavailability resulted in the selection of a 13-mer NPS oligonucleotide, GRN163, as a drug development candidate."( A novel telomerase template antagonist (GRN163) as a potential anticancer agent.
Akinaga, S; Asai, A; Chin, AC; Gryaznov, S; Harley, CB; Kusaka, H; Li, S; Oshima, Y; Piatyszek, M; Pongracz, K; Pruzan, R; Uochi, TA; Wunder, E; Yamamoto, Y; Yamashita, Y, 2003
)
0.32
" IKBL encodes a protein resembling members of the IkappaB protein family that regulate bioavailability of NFkappaB."( A promoter polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes.
Allcock, RJ; Boodhoo, A; Lee, S; Price, P; Voon, D; Williamson, D; Wong, AM, 2004
)
0.32
" Their affinity and specificity for a given protein make it possible to isolate a ligand to virtually any target, and adjusting their bioavailability expands their clinical utility."( Aptamers: an emerging class of therapeutics.
Nimjee, SM; Rusconi, CP; Sullenger, BA, 2005
)
0.33
" A novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4, platelet-derived growth factor receptor, and Kit receptors in preclinical models."( AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts.
Alva, G; Bready, J; Cattley, R; Chen, D; Coxon, A; DeMelfi, T; Diaz, Z; Estrada, J; Gan, Y; Kaufman, S; Kendall, R; Kumar, G; Meyer, J; Montestruque, S; Neervannan, S; Patel, V; Polverino, A; Radinsky, R; Starnes, C; Talvenheimo, J; Tasker, A; Wang, L, 2006
)
0.33
"AMG 706 is an investigational, orally bioavailable inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and stem-cell factor receptor."( Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.
Bass, MB; Benjamin, R; Chang, DD; Herbst, RS; Koutsoukos, A; Kurzrock, R; Mulay, M; Ng, C; Polverino, A; Purdom, M; Rosen, LS; Silverman, J; Sun, YN; Van Vugt, A; Wiezorek, JS; Xu, RY, 2007
)
0.34
" In vivo, these compounds show good bioavailability and efficient biodistribution to all major organs, while exerting acceptable toxicity at therapeutically relevant doses."( Oligonucleotide n3'-->p5' phosphoramidates and thio-phoshoramidates as potential therapeutic agents.
Gryaznov, SM, 2010
)
0.36
" Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations."( Motesanib and advanced NSCLC: experiences and expectations.
Blumenschein, GR; Raghav, KP, 2011
)
0.37
"The purpose of this study was to employ a nanoscale liposomal carrier to resolve the delivery problem, and increase the bioavailability and efficiency of pTT."( Topical delivery of DNA oligonucleotide to induce p53 generation in the skin via thymidine dinucleotide (pTT)-encapsulated liposomal carrier.
Fang, YP, 2011
)
0.37
"Various chemical drug delivery vehicles have been developed aiming at improving the bioavailability of nucleic acid-based drugs."( Use of cell-penetrating-peptides in oligonucleotide splice switching therapy.
El Andaloussi, SA; Hammond, SM; Mäger, I; Wood, MJ, 2012
)
0.38
" In particular small interfering RNAs (siRNAs) are being rapidly recognized as promising therapeutic tools, but their poor bioavailability limits the full realization of their clinical potential."( Exosomes for targeted siRNA delivery across biological barriers.
El Andaloussi, S; Lakhal, S; Mäger, I; Wood, MJ, 2013
)
0.39
" Systemic bioavailability was minimal, and no systemic toxicity was observed at exposure levels appreciably above pharmacological doses and doses proposed for clinical trials."( Local and systemic tolerability of a 2'O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-α delivery by inhalation in mouse and monkey.
Fey, RA; Gigliotti, AP; Henry, SP; Hutt, JA; McDonald, JD; Reed, MD; Templin, MV; Yu, RZ, 2014
)
0.4
"Poor cellular delivery and low bioavailability of novel potent therapeutic molecules continue to remain the bottleneck of modern cancer and gene therapy."( Peptide-mediated delivery: an overview of pathways for efficient internalization.
Pae, J; Pooga, M, 2014
)
0.4
" Clinical translation of ONs is hampered by the inadequate bioavailability in the target cells due to the substantial extracellular and intracellular barriers exposed to these molecules."( Sequence-defined polymers for the delivery of oligonucleotides.
Lehto, T; Wagner, E, 2014
)
0.66
" In recent years, small interfering RNA (siRNA) has emerged as promising therapeutic alternative for diseases with gene-based pathophysiology, however poor bioavailability limits its therapeutic potential."( Exosomes: Natural Carriers for siRNA Delivery.
Gupta, V; Kumar, L; Vaidya, B; Verma, S, 2015
)
0.42
" Despite their undoubted potential, clinical translation of these molecules, however, has been largely held back by their limited bioavailability in the target tissues/cells."( Peptides for nucleic acid delivery.
El Andaloussi, S; Ezzat, K; Lehto, T; Wood, MJA, 2016
)
0.43
" These CPPs typically deliver their cargoes into cells by an endosomal-dependent mechanism resulting in lower bioavailability of the cargo."( CLIP6-PNA-Peptide Conjugates: Non-Endosomal Delivery of Splice Switching Oligonucleotides.
Karni, R; Mogilevsky, M; Soudah, T; Yavin, E, 2017
)
0.69
" The latest technological advances in oligonucleotide therapeutics utilizes direct conjugation to targeting ligands, which has improved bioavailability and target tissue exposure many-fold."( Recent preclinical and clinical advances in oligonucleotide conjugates.
Abrams, M; Amiji, M; Craig, K, 2018
)
0.48
" We highlighted that inhibition of miR-199a-3p and -5p independently increases NO bioavailability by promoting eNOS activity and reducing its degradation, thereby supporting VEGF-induced endothelial tubulogenesis and modulating vessel contractile tone."( MicroRNA-199a-3p and MicroRNA-199a-5p Take Part to a Redundant Network of Regulation of the NOS (NO Synthase)/NO Pathway in the Endothelium.
Balligand, JL; Catalucci, D; Condorelli, G; Dessy, C; Di Mauro, V; Esfahani, H; Gomez, EL; Joris, V; Lobysheva, I; Menchi, L, 2018
)
0.48
"In vivo bioavailability and delivery of nucleic acids to the site of action is a severe limitation in oligonucleotide (ON) therapeutics."( Attachment of Peptides to Oligonucleotides on Solid Support Using Copper(I)-Catalyzed Huisgen 1,3-Dipolar Cycloaddition.
Honcharenko, D; Honcharenko, M; Strömberg, R, 2019
)
0.81
"The oral bioavailability of therapeutic proteins is limited by the gastrointestinal barriers."( Lyophilisation Improves Bioactivity and Stability of Insulin-Loaded Polymeric-Oligonucleotide Nanoparticles for Diabetes Treatment.
Al-Salami, H; Dass, CR; Wong, CY, 2020
)
0.56
" However, their high molecular weight limits their bioavailability for otherwise-treatable neurological disorders."( Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy.
Abendroth, F; Ahlskog, N; Burrell, M; Gait, MJ; Goli, L; Gurrell, I; Hammond, SM; Stoodley, J; Thom, G; Webster, CI; Wood, MJ, 2022
)
0.72
" Here, we show that the well-tolerated and orally bioavailable synthetic sphingolipid analog, SH-BC-893, increases the activity of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) up to 200-fold in vitro without permeabilizing endosomes."( Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.
Anderson, BA; Eckenstein, KH; Edinger, AL; Finicle, BT; Fruman, DA; Gil, D; Hanessian, S; McCracken, AN; Revenko, AS; Seth, PP; Wan, WB, 2023
)
1.11

Dosage Studied

Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the central nervous system. This dosing regime is higher than a patient would be expected to receive in the clinical use of ASOs.

ExcerptRelevanceReference
" These genes would be expected to be expressed in females from both active and inactive X chromosomes to ensure correct dosage of gene product."( X-chromosome inactivation may explain the difference in viability of XO humans and mice.
Ashworth, A; Kay, G; Lovell-Badge, R; Rastan, S, 1991
)
0.28
" Cells were treated in a dose-response manner for 72 hr and the concentration of drug necessary to inhibit cell growth 50% (GI50) was determined."( Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells.
Hubbell, HR; Lee, C; Pequignot, EC; Suhadolnik, RJ; Willis, DH, 1985
)
0.27
" Loss of these adducts from liver DNA was observed to exhibit a triphasic profile: rapid loss during the first 24 h (t 1/2 = 12 h) followed by a slower decline from 1 to 14 days post dosing (t 1/2 = 7 days) and an extremely slow decline from days 14 to 105 post treatment (t 1/2 = 109 days)."( Formation and persistence of sterigmatocystin--DNA adducts in rat liver determined via 32P-postlabeling analysis.
Irvin, TR; Randerath, K; Reddy, MV, 1985
)
0.27
" There was no general dose-response correlation between the induction of (2',5')oligo(A) synthetase and the cytostatic activity of interferon treatment alone or in combination with double-stranded RNA."( Effects of fibroblast and recombinant leukocyte interferons and double-stranded RNA on ppp(2'-5')An synthesis and cell proliferation in human colon carcinoma cells in vitro.
Chapekar, MS; Glazer, RI, 1983
)
0.27
" The oral route of drug dosing offers many advantages over other possible routes when chronic drug administration is necessary."( Radiolabeling of methylphosphonate and phosphorothioate oligonucleotides and evaluation of their transport in everted rat jejunum sacs.
Avrutskaya, AV; Brouwer, KL; Hughes, JA; Juliano, RL; Wickstrom, E, 1995
)
0.54
" In any given transfection, a 100-fold variation in oligonucleotide dosage was found."( Antisense DNA downregulation of the ERBB2 oncogene measured by a flow cytometric assay.
Babiss, LE; Caruthers, MH; Davis, P; Demirdji, S; Iglehart, JD; Marks, JR; Vaughn, JP, 1995
)
0.29
" Pre-IND conduct of pharmacodynamic cardiovascular screening is highly recommended for defining safe clinical dosing regimens for phosphorothioate (and, possibly, other charged-backbone) oligomers."( Regulatory considerations for oligonucleotide drugs: updated recommendations for pharmacology and toxicology studies.
Ahn, CH; Black, LE; Cavagnaro, JA; DeFelice, AF; DeGeorge, JJ; Farrelly, JG; Jordan, A; Taylor, AS, 1994
)
0.29
" This stimulation was mediated by ER, because 1) dose-response curves established with tamoxifen and hydroxytamoxifen were in agreement with their affinity for ER; 2) when present with antiestrogens, estradiol abolished this phenomenon; and 3) this effect was not observed in MDT (ER-negative) cells."( Prolonged treatment of breast cancer cells with antiestrogens increases the activating protein-1-mediated response: involvement of the estrogen receptor.
Astruc, ME; Bali, P; Chabret, C; Gagne, D; Pons, M, 1995
)
0.29
" However, dose-response experiments using various truncations of the p21 ras-derived peptide revealed that the peptide fine specificities of the five TCCs were not completely identical."( Heterogeneity of T cells specific for a particular peptide/HLA-DQ complex.
Gaudernack, G; Gedde-Dahl, T; Hansen, T; Spurkland, A; Thorsby, E; Vartdal, F, 1994
)
0.29
" There was a linear dose-response relationship between thrombin aptamer infusion rate and prolongation of plasma prothrombin time."( In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits.
Bock, LC; Griffin, LC; Leung, LL; Tidmarsh, GF; Toole, JJ, 1993
)
0.29
"The distribution of a model 16-mer oligothymidylate (pdT16) in several ocular tissues (cornea, conjunctiva, sclera, iris, lens, aqueous and vitreous humors) was determined after instillation in the eye of various dosage forms in a rabbit model."( Comparison of the ocular distribution of a model oligonucleotide after topical instillation in rabbits of conventional and new dosage forms.
Bochot, A; Couvreur, P; Fattal, E; Mashhour, B; Puisieux, F, 1998
)
0.3
" Its ED50 is estimated to be 80 pmol/kg in preinjection dose-response experiments, compared with 4 pmol/kg for the dimeric anti-L-selectin antibody DREG56."( Anti-L-selectin aptamers: binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo.
Chang, YF; O'Connell, D; Parma, DH; Ringquist, S; Watson, SR; Weigand, L, 2000
)
0.31
" We investigated the optimal LJP 394 dosing regimen required to maximally reduce serum dsDNA antibodies."( Treatment of systemic lupus erythematosus with LJP 394.
Aranow, C; Berner, CM; Cash, JM; Coutts, S; Cronin, ME; de Haan, HA; Furie, RA; Hudson, NP; Katz, RS; Liebling, MR; Weisman, MH, 2001
)
0.31
" After a 2 month pretreatment period, dosing visits continued for 16 weeks, after which there was a 2 month posttreatment period."( Treatment of systemic lupus erythematosus with LJP 394.
Aranow, C; Berner, CM; Cash, JM; Coutts, S; Cronin, ME; de Haan, HA; Furie, RA; Hudson, NP; Katz, RS; Liebling, MR; Weisman, MH, 2001
)
0.31
" The former pathway was clearly the most important, and all reaction products exhibited a dose-response relationship."( Characterization of DNA damage at purine residues in oligonucleotides and calf thymus DNA induced by the mutagen 1-nitrosoindole-3-acetonitrile.
Gatehouse, D; Jones, GD; Lucas, LT; Shuker, DE, 2001
)
0.56
" Significant correlations were found between the numbers of alleles encoding decreased metabolism and nortriptyline plasma concentration, nortriptyline dose, and nortriptyline plasma concentration standardized for dose, indicating a gene dosage effect."( CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression.
Cheuk, W; Kirshner, MA; Mulsant, BH; Murphy, GM; Pascoe, N; Pollock, BG; Reynolds, CF, 2001
)
0.31
" Uptake followed a dose-response curve."( Uptake and quantification of intracellular concentration of lipophilic pro-oligonucleotides in HeLa cells.
Bologna, JC; Imbach, JL; Morvan, F; Vivès, E, 2002
)
0.54
"We have evaluated the specificity and the variation in activity against human immunodeficiency virus (HIV) infection of antisense oligodeoxynucleotides (ODNs) with regard to factors such as dose-response range, number and choice of experimental controls, backbone modifications of the ODNs, type of cell infection, length of assays, and delivery approach."( Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?
Lavigne, C; Sauve, G; Thierry, AR; Yelle, J, 2002
)
0.31
" Since high levels of the enzyme confer the efficient repair of DNA alkylation, the chemotherapeutic potential of alkylating chemicals can be maintained either increasing drug dosage or reducing the amount of endogenous MGMT."( The sensitivity of MCF10A breast epithelial cells to alkylating drugs is enhanced by the inhibition of O6-methylguanine-DNA methyltransferase transcription with a synthetic double strand DNA oligonucleotide.
Citti, L; Colombo, MG; Mariani, L; Piccirilli, A; Poliseno, L; Rainaldi, G, 2002
)
0.31
" In addition to the splicing factors, SSD1, BTS1, and BET4 were identified as dosage suppressors of clf1Delta2 or selected slc mutants."( Genetic interactions with CLF1 identify additional pre-mRNA splicing factors and a link between activators of yeast vesicular transport and splicing.
Hobbs, K; Jay, S; Rymond, BC; Vincent, K; Wang, Q, 2003
)
0.32
"GEM231 administered as a continuous infusion is safe; however, continuous protracted dosing is limited by ST elevations."( A safety study of a mixed-backbone oligonucleotide (GEM231) targeting the type I regulatory subunit alpha of protein kinase A using a continuous infusion schedule in patients with refractory solid tumors.
Agrawal, S; Bulgaru, A; Desai, K; Fields, A; Goel, S; Goldberg, G; Grindel, M; Mani, S; Martin, R, 2003
)
0.32
" Seventeen base PNA or LNA oligomers targeting different regions of the HCV IRES demonstrated a sequence-specific dose-response inhibition of translation with EC(50) values of 50-150 nM."( Intracellular inhibition of hepatitis C virus (HCV) internal ribosomal entry site (IRES)-dependent translation by peptide nucleic acids (PNAs) and locked nucleic acids (LNAs).
Corey, D; Nulf, CJ, 2004
)
0.32
" By integrating the XLnt system with an assay design separating probe/target immobilization and signal elaboration functions, relative gene dosage assessment can be applied to the quantitation of fractional resistance to methylation-sensitive restriction enzyme (MSRE) digestion."( Photocrosslinking oligonucleotide hybridization assay for concurrent gene dosage and CpG methylation analysis.
Peoples, R; Van Atta, R; Wood, M, 2004
)
0.32
"This quorum-sensing-derived mammalian transgene control system (Q-ON) enabled precise SCB1-specific fine-tuning of (i) desired transgene transcription in a variety of mammalian/human cell lines and human primary cells, (ii) small interfering RNA-mediated posttranscriptional knockdown (siRNA) in mammalian cells, and (iii) dosing of a human glycoprotein in mice."( Engineered Streptomyces quorum-sensing components enable inducible siRNA-mediated translation control in mammalian cells and adjustable transcription control in mice.
Aubel, D; de Jesus, M; El-Baba, MD; Fussenegger, M; Keller, B; Malphettes, L; Schoenmakers, R; Spielmann, M; van de Wetering, P; Weber, CC; Weber, W; Wurm, FM, 2005
)
0.33
"In the combined analysis of the primary end point (for a total of 1186 patients), efficacy was demonstrated, without a dose-response relationship, for all three doses of pegaptanib (P<0."( Pegaptanib for neovascular age-related macular degeneration.
Adamis, AP; Cunningham, ET; Feinsod, M; Gragoudas, ES; Guyer, DR, 2004
)
0.32
" We have used a model DNA containing a bulge, formed by five mismatched bases, and have observed a linear dose-response for the formation of strand breaks on the single-stranded regions of both the brominated strand and the opposite nonbrominated strand."( Interstrand cross-links: a new type of gamma-ray damage in bromodeoxyuridine-substituted DNA.
Cecchini, S; Girouard, S; Huels, MA; Hunting, DJ; Sanche, L, 2005
)
0.33
" Under these conditions, mRNA target reduction dose-response curves were also shifted to lower doses."( Transfection protocol for antisense oligonucleotides affects uniformity of transfection in cell culture and efficiency of mRNA target reduction.
Bennett, CF; Freier, S; Lollo, B; Peralta, ER; Reed, CA; Wenrich, LM; Wong, CA, 2005
)
0.6
" Analysis of transgenic mice suggested that synoviolin gene dosage is implicated in the pathogenesis of arthropathy."( Identification of a crucial site for synoviolin expression.
Amano, T; Aratani, S; Fujita, H; Fukamizu, A; Izumi, T; Ji, F; Kato, Y; Kawahara, K; Komiya, S; Maruyama, I; Nakajima, T; Nishioka, K; Sugamiya, A; Sugiura, A; Tsuchimochi, K; Yagishita, N; Yamasaki, S, 2005
)
0.33
") dosing of ISIS 2105, a 20-base phosphorothioate oligonucleotide, in timed-pregnant Sprague-Dawley rats."( Maternal and fetal distribution of a phosphorothioate oligonucleotide in rats after intravenous infusion.
de Peyster, A; Geary, R; Levin, AA; Riley, JP; Soucy, NV; Templin, MV, 2006
)
0.33
" This dosing regime is higher than a patient would be expected to receive in the clinical use of oligonucleotides."( Maternal and fetal distribution of a phosphorothioate oligonucleotide in rats after intravenous infusion.
de Peyster, A; Geary, R; Levin, AA; Riley, JP; Soucy, NV; Templin, MV, 2006
)
0.55
" The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice."( A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, IGF-I production and body weight gain in normal mice.
Baker, BF; Berdeja, A; d'Aniello, EM; Jarres, RA; Kerr, LM; Lofthouse, S; Rao, AM; Sioufi, NB; Tachas, G; Waters, MJ; Wraight, CJ, 2006
)
0.33
" Multiplex dosage pyrophosphorolysis-activated polymerization (MD-PAP), a derivative of PAP, was utilized to detect these types of mutations."( Multiplex dosage pyrophosphorolysis-activated polymerization: application to the detection of heterozygous deletions.
Li, X; Liu, Q; Nguyen, VQ; Sommer, SS, 2006
)
0.33
" These results indicate that a single dosing of CpG ODN-lipoplex is effective in inhibiting peritoneal dissemination and inducing long-lasting antitumor immunity."( Inhibition of peritoneal dissemination of tumor cells by single dosing of phosphodiester CpG oligonucleotide/cationic liposome complex.
Hashida, M; Hyoudou, K; Kuramoto, Y; Nishikawa, M; Yamashita, F, 2006
)
0.33
" Here, dose-response studies confirm a strong correlation between the suppression of phosphatase activity and cell death."( Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2Aalpha.
Aragon, IV; Bonness, K; Dean, NM; Honkanen, RE; Ofori-Acquah, S; Rutland, B, 2006
)
0.33
" The yields were determined and the dose-response curves explained by a mechanistic model consisting of three reaction pathways: (1) trappable-radical single-track, (2) trappable-radical multiple-track, and (3) molecular."( Mechanisms of direct radiation damage in DNA, based on a study of the yields of base damage, deoxyribose damage, and trapped radicals in d(GCACGCGTGC)(2).
Bernhard, WA; Gilbert, DC; Naumenko, KA; Purkayastha, S; Razskazovskiy, Y; Sharma, KK; Swarts, SG, 2007
)
0.34
" Further studies are indicated to determine optimal dosing in this population and to definitively address the question of relationship to graft patency."( Statins are independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia.
Beckman, JA; Belkin, M; Conte, MS; Hevelone, N; Owens, CD; Schanzer, A, 2008
)
0.35
" Dose-response studies indicated that optimal induction of CD80 expression was achieved with much lower concentrations of CpG ODN than optimal induction of proliferation."( Impaired naive and memory B-cell responsiveness to TLR9 stimulation in human immunodeficiency virus infection.
Harding, CV; Jiang, W; Lederman, MM; Mohner, RJ; Nedrich, TM; Rodriguez, B; Sieg, SF, 2008
)
0.35
" Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice."( Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.
Aguzzi, A; Bremer, J; Haybaeck, J; Heikenwalder, M; Krautler, NJ; Kurrer, MO; Tiberi, C, 2009
)
0.35
" Phosphorylation of ERK 1/2 induced by synthetic ODN is dose-response dependent, being maximal at 100 microg/ml."( Synthetic oligodeoxynucleotides induce MAP kinases activation in murine TIB-73 hepatocytes.
Chicano, A; García-Peñarrubia, P; Hernández-Caselles, T; Lizana, A; Martín-Orozco, E; Martínez-Esparza, M; Ruiz-Alcaraz, AJ, 2010
)
0.36
" Pharmacology studies in both mice and non-human primates were conducted with a 13-mer LNA oligonucleotide against apoB, and the data showed that repeated dosing of the 13-mer at 1-2 mg/kg/week was sufficient to provide a significant and long lasting lowering of non-high-density lipoprotein (non-HDL) cholesterol without increasing serum liver toxicity markers."( Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates.
Aarup, V; Fisker, N; Hansen, HF; Hansen, JB; Hedtjärn, M; Koch, T; Lindholm, MW; Rosenbohm, C; Straarup, EM; Ørum, H, 2010
)
0.64
" The population pharmacokinetic/pharmacodynamic model provides a tool for predicting tumor response to the drug to support the dosing regimen of motesanib in thyroid cancer patients."( Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.
Bruno, R; Claret, L; Kuchimanchi, M; Lu, JF; Melara, R; Sun, YN; Sutjandra, L, 2010
)
0.36
" Dose-response simulations were performed in patients with differentiated thyroid cancer."( Development of a modeling framework to simulate efficacy endpoints for motesanib in patients with thyroid cancer.
Bruno, R; Claret, L; Lu, JF; Sun, YN, 2010
)
0.36
" Overall, the integration of preclinical PK/PD data enabled to appropriately predict dose and dosing regimen of LY2181308 in humans with pharmacologically relevant survivin inhibition achieved at 750mg."( Integrated analysis of preclinical data to support the design of the first in man study of LY2181308, a second generation antisense oligonucleotide.
André, V; Burgess, M; Callies, S; Francis, P; Lahn, M; Patel, B; Waters, D, 2011
)
0.37
" Our approach decreased the need for extensive dose-response studies, reducing the duration, complexity and cost of clinical development."( Dose selection for a direct and selective factor IXa inhibitor and its complementary reversal agent: translating pharmacokinetic and pharmacodynamic properties of the REG1 system to clinical trial design.
Alexander, JH; Becker, RC; Chan, MY; Cohen, MG; Harrington, RA; Povsic, TJ; Rusconi, CP; Wargin, WA; Zelenkofske, SL, 2011
)
0.37
" In both studies, animals were dosed once weekly for 12 weeks up to the maximum feasible dose of 960 mg/kg per injection."( Chemical and mechanistic toxicology evaluation of exon skipping phosphorodiamidate morpholino oligomers in mdx mice.
Nelson, K; Ness, KP; Poage, D; Sazani, P; Shrewsbury, AS; Weller, DL, 2011
)
0.37
" These approaches however are rendered less effective owing to a lack of targeted delivery, as seen with lipid-conjugates, and the potential immune reactions due to repeated dosing with high molecular weight BSA conjugated TFO."( Targeted TFO delivery to hepatic stellate cells.
Mahato, RI; Singh, S; Yang, N, 2011
)
0.37
" LY2275796 pharmacokinetics supported the dosing regimen."( A phase 1 dose escalation, pharmacokinetic, and pharmacodynamic evaluation of eIF-4E antisense oligonucleotide LY2275796 in patients with advanced cancer.
André, V; Brail, L; Callies, S; Fishman, M; Holzer, TR; Hong, DS; Kadam, SK; Kurzrock, R; Meric-Bernstam, F; Naing, A; Nasir, A; Oh, Y; Simon, G; Wheler, J, 2011
)
0.37
" Compiled stochastic data (pathogen concentration, susceptible populations) and literature-obtained deterministic data (pathogen dose-response model parameter values) were used in estimating waterborne gastroenteritis burden."( Molecular techniques in ecohealth research toolkit: facilitating estimation of aggregate gastroenteritis burden in an irrigated periurban landscape.
Anceno, AJ; Houpt, ER; Icenhour, CR; Mason, CS; Sethabutr, O; Shipin, OV; Tserendorj, A, 2011
)
0.37
" On the other hand, the optimal combination and dosage of these drugs, selection of the apropriate biomarker and better understanding of the conflicting role of PDGFR and FGFR signaling in angiogenesis remain future challenges."( [Possibilities for inhibiting tumor-induced angiogenesis: results with multi-target tyrosine kinase inhibitors].
Döme, B; Török, S, 2012
)
0.38
" Four mipomersen (19%) and two placebo subjects (17%) discontinued dosing prematurely due to AEs."( Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial.
Baker, BF; Basart, DC; Beuers, UH; Donovan, JM; Geary, RS; Kastelein, JJ; Nederveen, AJ; Stroes, ES; Trip, MD; Verheij, J; Visser, ME; Wagener, G, 2012
)
0.38
" The reason was attributed that Fe(0) dosing enhanced the activity of fermentative bacteria, which played an important role in acidogenesis and decolorization."( Enhanced azo dye wastewater treatment in a two-stage anaerobic system with Fe0 dosing.
Chen, S; Li, Y; Liu, Y; Quan, X; Zhang, Y; Zhao, Z, 2012
)
0.38
" Future studies will explore alternative dosing schedules aimed at minimizing side effects."( Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.
Burgess, LJ; Ceska, R; Chasan-Taber, S; Gouni-Berthold, I; McGowan, MP; Soran, H; Tardif, JC; Wagener, G, 2012
)
0.38
" LY2181308 was administered with a loading dosage of three consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg."( Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML).
Andre, V; Andreeff, M; Brandt, JT; Callies, S; Erba, HP; Juckett, M; Kadam, S; Lahn, M; Sayar, H; Schmidt, S; Van Bockstaele, D, 2013
)
0.39
" Downmodulation of survivin mRNA and protein were assessed after single-agent dosing and decreased expression was observed in 2 of 5 patients with sufficient material for analysis."( A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA) antagonist, administered in combination with chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leu
Bhojwani, D; Bostrom, BC; Brown, P; Buchbinder, A; Carroll, WL; Cassar, J; Eckroth, E; Gaynon, P; Malvar, J; Morrison, D; Raetz, EA; Romanos-Sirakis, E; Sposto, R, 2014
)
0.4
"To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy."( Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.
Chin, W; Duell, PB; East, C; Guyton, JR; Mittleman, RS; Moriarty, PM; Santos, RD, 2015
)
0.42
" There were no significant changes in body weights between the groups during the dosing period, after the dosing interval or on the day of euthanasia."( Systemic administration of a cyclic signal transducer and activator of transcription 3 (STAT3) decoy oligonucleotide inhibits tumor growth without inducing toxicological effects.
Eiseman, J; Freilino, ML; Grandis, JR; Johnson, DE; Li, C; Li, H; Paul, K; Sen, M; Wang, L, 2014
)
0.4
" Using TR-FRET, we screened the Sigma LOPAC library for MBD2-MBD inhibitors and identified four compounds that also validated in a dose-response series."( Time-Resolved Fluorescence Resonance Energy Transfer Assay for Discovery of Small-Molecule Inhibitors of Methyl-CpG Binding Domain Protein 2.
Giovinazzo, H; Nelson, WG; Walker, D; Wyhs, N; Yegnasubramanian, S, 2014
)
0.4
"This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens."( Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers.
Baker, BF; Flaim, JD; Grundy, JS; Kastelein, JJ; McGowan, MP, 2014
)
0.4
" These results suggest that the dosage adjustment of warfarin or mipomersen is not expected to be necessary with coadministration."( Lack of clinical pharmacodynamic and pharmacokinetic drug-drug interactions between warfarin and the antisense oligonucleotide mipomersen.
Boltje, I; Grundy, JS; Hard, ML; Li, Z; Singh, T; von Moltke, LL, 2014
)
0.4
" The unique product characteristics of ONs require considerations when planning developmental and reproductive toxicology studies, including (a) chemical characteristics, (b) assessment of intended and unintended mechanism of action, and (c) the optimal exposure, including dosing regimen."( Considerations for assessment of reproductive and developmental toxicity of oligonucleotide-based therapeutics.
Berman, C; Campion, S; Cavagnaro, J; Henry, S; Kornbrust, D; White, T, 2014
)
0.4
" The aim of this study was to establish the sustained virological response rate to peginterferon (P) and ribavirin (R) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen."( Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients.
de Bruijne, J; Hodges, MR; Janssen, HL; Kupcova, V; Lawitz, EJ; Maan, R; Reesink, HW; Rodriguez-Torres, M; van der Meer, AJ; van der Ree, MH; van Vliet, A; Welzel, TM; Wiercinska-Drapalo, A; Zeuzem, S, 2014
)
0.4
" SVR was achieved in 7/12 patients previously dosed with miravirsen."( Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients.
de Bruijne, J; Hodges, MR; Janssen, HL; Kupcova, V; Lawitz, EJ; Maan, R; Reesink, HW; Rodriguez-Torres, M; van der Meer, AJ; van der Ree, MH; van Vliet, A; Welzel, TM; Wiercinska-Drapalo, A; Zeuzem, S, 2014
)
0.4
" In this review, a comprehensive discussion of the opportunities and challenges of intravaginal delivery are highlighted, in the context of the intravaginal environment and currently utilized dosage forms."( Protein and oligonucleotide delivery systems for vaginal microbicides against viral STIs.
Steinbach, JM, 2015
)
0.42
" Thus, the management of patients intolerant to statins, particularly those at high or very high cardiovascular risk, involves alternative therapies, including the switch to another statin or the use of intermittent dosage statin regimens, as well as nonstatin lipid lowering drugs (ezetimibe and fibrates) or new hypolipidemic drugs such as PCSK9 monoclonal antibodies, the antisense oligonucleotide against the coding region of human apolipoprotein B mRNA (mipomersen), and microsomal triglyceride transfer protein inhibitor lomitapide."( Statin intolerance: diagnosis and remedies.
Catapano, AL; Pirillo, A, 2015
)
0.42
" Notably, we establish that Pbx1 directly represses Pdgfrb, and demonstrate that decreased Pdgfrb dosage in conditional Pbx1 mutants substantially rescues vascular patterning defects and neonatal survival."( Pbx1-dependent control of VMC differentiation kinetics underlies gross renal vascular patterning.
Aho, R; Herzlinger, D; Hurtado, R; Kurylo, C; Liang, C; Mtui, J; Selleri, L; Zewdu, R, 2015
)
0.42
"To assess the plasma level of various miRNAs in patients dosed with miravirsen."( Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma.
de Bruijne, J; Janssen, HL; Kootstra, NA; Ottosen, S; Reesink, HW; van der Meer, AJ; van der Ree, MH; van Nuenen, AC, 2016
)
0.43
" Plasma levels of 179 miRNAs were determined by qPCR and compared between patients dosed with miravirsen or placebo."( Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma.
de Bruijne, J; Janssen, HL; Kootstra, NA; Ottosen, S; Reesink, HW; van der Meer, AJ; van der Ree, MH; van Nuenen, AC, 2016
)
0.43
"We demonstrated a substantial and prolonged decrease in plasma miR-122 levels in patients dosed with miravirsen."( Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma.
de Bruijne, J; Janssen, HL; Kootstra, NA; Ottosen, S; Reesink, HW; van der Meer, AJ; van der Ree, MH; van Nuenen, AC, 2016
)
0.43
" Tumor-associated macrophages, B cells, dendritic cells, and cytotoxic T cells were increased, T regulatory cells were not induced, and long-term GL261 glioma regression with immune memory was achieved when CpG-1826 was combined with either single cyclophosphamide dosing (90 mg/kg) or metronomic cyclophosphamide treatment (two cycles at 45 mg/kg, spaced 12-days apart)."( CpG-1826 immunotherapy potentiates chemotherapeutic and anti-tumor immune responses to metronomic cyclophosphamide in a preclinical glioma model.
Jordan, M; Waxman, DJ, 2016
)
0.43
" Dosing was once weekly for 72 weeks."( Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.
Buyse, G; Campion, G; de Kimpe, SJ; Goemans, NM; Kroksmark, AK; Lourbakos, A; Tulinius, M; van den Hauwe, M; van Deutekom, JC; Wilson, RJ, 2016
)
0.43
"4 years of dosing for most patients."( Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.
Buyse, G; Campion, G; de Kimpe, SJ; Goemans, NM; Kroksmark, AK; Lourbakos, A; Tulinius, M; van den Hauwe, M; van Deutekom, JC; Wilson, RJ, 2016
)
0.43
" However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed."( MicroRNA-targeted therapeutics for lung cancer treatment.
Cho, WC; Liu, X; Luo, M; Xue, J; Yang, J, 2017
)
0.46
" For the first time, we showed similar and dose-dependent effects on the coagulation and complement cascade after intravenous dosing similar to those observed in NHPs."( From the Cover: The Minipig is a Suitable Non-Rodent Model in the Safety Assessment of Single Stranded Oligonucleotides.
Albassam, M; Altmann, B; Berrera, M; Brady, K; Braendli-Baiocco, A; Constien, R; Dumong Erichsen, K; Festag, M; Fisker, N; Funk, J; Lenz, B; Mihatsch, MJ; Mohr, S; Persson, R; Ploix, C; Schmitt, G; Schuler, F; Singer, T; Tessier, Y; Weiser, T, 2017
)
0.67
" This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord."( Pharmacology, pharmacokinetics, and metabolism of the DNA-decoy AYX1 for the prevention of acute and chronic post-surgical pain.
Donahue, RR; Eddinger, K; Harris, S; Klukinov, M; Mamet, J; Manning, DC; Taylor, BK; Yaksh, T; Yeomans, DC, 2017
)
0.46
" No evidence of tolerization or amplification of responses was evident on repeated dosing and 15."( First-in-Human Study With the Inhaled TLR9 Oligonucleotide Agonist AZD1419 Results in Interferon Responses in the Lung, and Is Safe and Well-Tolerated.
Bell, J; Campbell, JD; Candia, AF; Coffman, RL; Delaney, S; Floettmann, S; Fuhr, R; Hessel, EM; Jackson, S; Keeling, D; Kell, S; Lum, J; McHale, M; Robinson, I; Traquina, P; Wong, C, 2018
)
0.48
" These advances with versatile, preassembled reagents could greatly reduce the time and cost of in vitro or ex vivo gene-editing applications in precision medicine and drug discovery and aid in the development of increased and serial dosing regimens for somatic gene editing in vivo."( Assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an RNA aptamer for precise gene editing.
Abdeen, AA; Carlson-Stevermer, J; Goedland, M; Kohlenberg, L; Lou, M; Molugu, K; Saha, K, 2017
)
0.7
" Groups of citizens (from 2-6 people per group) attended a short demonstration of a microneedle biosensor and automated dosing system versus a traditional phlebotomy approach over a two-day public festival."( Public acceptability of computer-controlled antibiotic management: An exploration of automated dosing and opportunities for implementation.
Cass, AE; Freeman, DM; Georgiou, P; Gowers, SA; Herrero, P; Holmes, AH; Ming, D; O'Hare, D; Rawson, TM, 2019
)
0.51
" Besides, the inhibition of miR-122 lasted for 28 days with limited dosage in vivo."( Simple and rational design of a polymer nano-platform for high performance of HCV related miR-122 reduction in the liver.
Ding, L; Duan, Y; Fu, H; Huang, L; Liu, L; Shen, M; Sun, Y; Wang, Q; Zhang, L; Zhang, X, 2018
)
0.48
" However, specific issues regarding the in vivo use of miRNA inhibitors (antimiRs) such as organ-specific delivery, optimal dosing and formulation of the best chemistry to obtain efficient miRNA inhibition remain to be addressed."( Comparison of different chemically modified inhibitors of miR-199b in vivo.
Bitsch, N; da Costa Martins, PA; de Windt, LJ; Duygu, B; Juni, R; Ottaviani, L; Wit, JBM, 2019
)
0.51
" We assessed the efficacy and safety of two mipomersen dosing regimens in HeFH patients and explored whether thrice-weekly dosing improves the benefit-risk profile."( Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia.
Ballantyne, CM; Catapano, AL; Duell, PB; Kastelein, JJP; Moriarty, PM; Reeskamp, LF; Santos, RD, 2019
)
0.51
" The thrice-weekly dosing regimen was associated with lower frequency of flu-like symptoms, which might help avert discontinuation in some patients, but otherwise had no major benefits."( Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia.
Ballantyne, CM; Catapano, AL; Duell, PB; Kastelein, JJP; Moriarty, PM; Reeskamp, LF; Santos, RD, 2019
)
0.51
" Population PK modelling was conducted using data from 3 available danvatirsen Phase I/II studies in oncology patients to investigate the impact of flat dosing on exposure compared to ideal body weight-based dosing."( Population pharmacokinetic analysis of danvatirsen supporting flat dosing switch.
Al-Huniti, N; Arfvidsson, C; Cook, C; Lyne, P; Mugundu, G; Pease, E; Scott, ML; Tong, X; Xu, H; Zhou, D, 2019
)
0.51
"Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients."( Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis.
Boff, M; Bouisset, F; Cipolli, M; De Boeck, K; den Hollander, W; Drevinek, P; Elborn, JS; Henig, N; Montgomery, S; Paquette-Lamontagne, N; Perquin, J; Pressler, T; Schwarz, C; Tomkinson, N, 2020
)
0.56
" In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs."( Antisense Oligonucleotide Therapies for Neurodegenerative Diseases.
Bennett, CF; Cleveland, DW; Krainer, AR, 2019
)
0.51
" Notably, in an effort to reduce overall dosage and provide safer transition to the clinic, cooperative systems composed of two or more discrete nanomaterials have been recently proposed as an alternative to intrinsically multifunctional nanoparticles."( Decoding Live Cell Interactions with Multi-Nanoparticle Systems: Differential Implications for Uptake, Trafficking, and Gene Regulation.
Barman, I; Liang, L; Liu, Z, 2019
)
0.51
" Treatment of SMA with nusinersen is based on a fixed dosing regimen."( Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen.
Bolz, S; Hagenacker, T; Kizina, K; Kleinschnitz, C; Schlag, M; Stolte, B; Thimm, A; Totzeck, A, 2019
)
0.51
" A low dosage of loaded DTX in FA-CD@PP-CpG can promote infiltration of CTLs to improve efficacy of anti-PD-L1 antibody (aPD-L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy."( Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers.
Chen, L; Dong, C; Han, Y; Hu, X; Liang, S; Lin, Y; Liu, J; Lu, Y; Shi, S; Wang, C; Yao, T; Zhou, L, 2019
)
0.51
" When dosed orally in mice, only a small fraction (about 1% of total administered dose) of LNA ASOs was recovered in the peripheral tissues liver and kidney, however, no significant reduction in target gene expression (i."( Evaluation of bovine milk extracellular vesicles for the delivery of locked nucleic acid antisense oligonucleotides.
Alex, R; Berrera, M; Ducret, A; Duschmalé, M; Gamboni, R; Grossen, P; Huber, S; Jagasia, R; Jensen, ML; Keller, M; Koller, E; Kusznir, EA; Lauer, ME; Minz, T; Nordbo, B; Pandya, NJ; Portmann, M; Ringler, P; Sewing, S; Sladojevich, F; van Geijtenbeek, SK, 2021
)
0.84
"Onasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019."( Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy.
Battista, V; Flickinger, J; Jones, JN; Kichula, EA; Matesanz, SE, 2021
)
0.62
" Simulations demonstrated that the impact of a one-time delay in dosing or a missed dose on median cerebrospinal fluid exposures depended on duration of interruption and the regimen phase in which it occurred."( Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Berger, Z; East, L; Farrar, MA; Farwell, W; Finkel, RS; Kirschner, J; MacCannell, D; Mercuri, E; Muntoni, F; Nestorov, I; Peng, J; Zhou, J, 2021
)
0.62
" Four male rats per group were dosed once, 3, or 6 times subcutaneously, with 7 days between dosing, and sacrificed 3 days after the last dose."( Safety, Tissue Distribution, and Metabolism of LNA-Containing Antisense Oligonucleotides in Rats.
Braendli-Baiocco, A; Brink, A; Dzygiel, P; Festag, M; Fischer, G; Hetzel, U; Husser, C; Kipar, A; Koller, E; Lenz, B; Mihatsch, MJ; Romero-Palomo, F; Schadt, S; Sewing, S; Steinhuber, B; Tessier, Y; Winter, M, 2021
)
0.85
" The implanted port permits dosing in an outpatient setting and avoids the need for multiple future radiologic procedures, and it reduces discomfort, procedural costs and potential risks and sequelae of multiple anesthetics and radiation exposures."( Intrathecal catheter and port placement for nusinersen infusion in children with spinal muscular atrophy and spinal fusion.
Berde, CB; Padua, HM; Shashi, KK; Stone, SSD, 2021
)
0.62
" Collected data included medical history, dosage and administration, and AEs."( Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database.
Hoshino, M; Makioka, H; Matsuda, N; Nakamura, G; Takasaki, S; Wataya, T, 2023
)
0.91
" The most common approved dosing regimen is four intrathecal loading doses of nusinersen 12 mg; the first three are administered at 14-day intervals followed by a fourth dose 30 days later, and then 12-mg maintenance doses are administered every 4 months thereafter."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
"The objective of this report is to describe dosing regimens that allow for the most rapid restoration of steady-state concentrations of nusinersen in the cerebrospinal fluid (CSF) following a treatment interruption during maintenance dosing."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
" Potential dosing regimens for re-initiation of nusinersen were evaluated, with the goal of achieving the quickest restoration of steady-state nusinersen CSF concentrations without exceeding maximal CSF exposures observed during the initial loading period."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
"Our pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
" Some people may miss dose(s) or may stop nusinersen treatment at some point during maintenance dosing and then may want to continue treatment."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
0.72
" The patients were already in the maintenance phase of the dosing protocol and were prospectively evaluated for US-guided transforaminal approach."( Ultrasound-guided transforaminal approach for nusinersen delivery in adult spinal muscle atrophy patients with challenging access.
Salapura, V; Snoj, Ž, 2022
)
0.72
" The chemical structures, dosage forms, and sites and routes of administration are the principal determinants of ADME profiles and consequent impacts on their efficacy and ADRs."( Absorption, Distribution, Metabolism, and Excretion of US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.
Bahal, R; Gogate, A; Liu, A; Liu, S; Manautou, JE; Migliorati, JM; Nair, S; Rasmussen, TP; Zhong, XB, 2022
)
0.72
" In seven patients, dosing frequency was reduced to every 2 weeks due to recurrent thrombocytopenia."( Real-life experience with inotersen in hereditary transthyretin amyloidosis with late-onset phenotype: Data from an early-access program in Italy.
Antonini, G; Di Paolantonio, A; Gentile, L; Grandis, M; Leonardi, L; Lozza, A; Luigetti, M; Manganelli, F; Maria Pennisi, E; Mazzeo, A; Mussinelli, R; My, F; Obici, L; Romozzi, M; Russo, M; Sabatelli, M; Salvalaggio, A; Tagliapietra, M; Tozza, S, 2022
)
0.72
" Most patients followed the dosing schedule across the loading and maintenance dose periods."( Real-world Adherence to Nusinersen in Adults with Spinal Muscular Atrophy in the US: A Multi-site Chart Review Study.
Ajroud-Driss, S; Cartwright, MS; Chandak, A; Choi, JM; Elman, L; Frey, MR; Heiman-Patterson, T; Khachatryan, A; Martinez, M; McCormick, ME; Michelson, D; Paradis, AD; Proud, CM; Youn, B, 2022
)
0.72
" Additional advantages include the comparably simple and cost-effective way of manufacturing and the long dosing intervals."( RNA-targeted therapeutics in cardiovascular disease: the time is now.
Granger, CB; Krychtiuk, KA; Rader, DJ, 2022
)
0.72
"To assess the effect of pelacarsen, including monthly dosing of 80 mg, in subjects of Japanese ancestry."( Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects.
Hoenlinger, A; Hurh, E; Karwatowska-Prokopczuk, E; Lesogor, A; Margolskee, A; Tsimikas, S; Xia, S; Yan, JH,
)
0.13
" While the optimum dosage and total body clearance of MTX usually varies between individuals and even low-dose MTX has side effects, high-dose MTX may cause life-threatening side effects."( Ultrasensitive therapeutic drug monitoring of methotrexate by a structure-switching aptamer with cascade primer exchange reaction.
He, J; Shi, G; Wang, J; Zhang, M, 2023
)
0.91
" The developed population PK/PD model was robust to predict the dose-response relationships."( A population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis of vupanorsen from phase I and phase II studies.
Ahn, JE; Liu, J; Terra, SG, 2023
)
0.91
"Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the central nervous system (CNS)."( A single-cell map of antisense oligonucleotide activity in the brain.
Dubinsky, D; Gentile, JE; Jones, N; Kordasiewicz, HB; Maldonado, S; Minikel, EV; Mortberg, MA; Nadaf, NM; Petersen, CL; Simmons, S; Slamin, A; Vallabh, SM; Vanderburg, C; Zhao, HT, 2023
)
1.31
" Wearable monitoring of vancomycin could improve patient care by allowing targeted drug dosing within its narrow clinical window of safety and efficacy."( Microneedle electrochemical aptamer-based sensing: Real-time small molecule measurements using sensor-embedded, commercially-available stainless steel microneedles.
Bennett, H; Bolotsky, A; Downs, AM; Miller, PR; Polsky, R; Weaver, BM; Wolff, N, 2023
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (22,190)

TimeframeStudies, This Drug (%)All Drugs %
pre-19903067 (13.82)18.7374
1990's3888 (17.52)18.2507
2000's7280 (32.81)29.6817
2010's5774 (26.02)24.3611
2020's2181 (9.83)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 79.57

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index79.57 (24.57)
Research Supply Index10.06 (2.92)
Research Growth Index4.72 (4.65)
Search Engine Demand Index150.91 (26.88)
Search Engine Supply Index2.03 (0.95)

This Compound (79.57)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials245 (1.06%)5.53%
Reviews1,629 (7.04%)6.00%
Case Studies102 (0.44%)4.05%
Observational22 (0.10%)0.25%
Other21,130 (91.36%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]