Compounds > efaproxiral
Page last updated: 2024-11-07

efaproxiral

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

Description

Efaproxiral is a small-molecule drug that acts as a selective inhibitor of the enzyme pyruvate dehydrogenase kinase (PDK). PDK is responsible for inhibiting pyruvate dehydrogenase (PDH), a key enzyme in the metabolism of glucose. By inhibiting PDK, efaproxiral increases PDH activity, leading to increased glucose oxidation and ATP production. This has been shown to have beneficial effects in various preclinical studies, including models of diabetes, obesity, and heart failure. Efaproxiral is currently in clinical trials for the treatment of type 2 diabetes. Its potential benefits include improving glucose tolerance, reducing insulin resistance, and improving cardiovascular outcomes. Research into efaproxiral continues, with ongoing efforts to understand its mechanism of action in greater detail and explore its potential therapeutic applications in other diseases.'

efaproxiral: RN & structure given in first source; allosteric effector of hemoglobin [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID122335
CHEMBL ID18901
SCHEMBL ID1649963
MeSH IDM0184736

Synonyms (45)

Synonym
AC-5018
efaproxyn
rsr-13
131179-95-8
D03961
efaproxiral (usan/inn)
2-{4-[(3,5-dimethylanilino)-carbonyl-methyl]-phenoxy}-2-methylpropionic acid
RQ3 ,
2-(4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy)-2-methylpropionic acid
efaproxiral [usan:inn]
2-(4-((3,5-dimethylphenyl)amino)-2-oxoethyl)phenoxy)-2-methylpropanic acid
efaproxiral
2-dacmpp
propanoic acid, 2-(4-(2-((3,5-dimethylphenyl)amino)-2-oxoethyl)phenoxy)-2-methyl-
rsr 13
rsr13
DB08486
CHEMBL18901
FT-0667823
2-[4-[2-(3,5-dimethylanilino)-2-oxoethyl]phenoxy]-2-methylpropanoic acid
j81e81g364 ,
unii-j81e81g364
2-(4-(2-((3,5-dimethylphenyl)amino)-2-oxoethyl)phenoxy)-2-methylpropanoic acid
AKOS016003776
efaproxiral [usan]
efaproxiral [mi]
efaproxiral [inn]
efaproxiral [who-dd]
efaproxiral [mart.]
2-[4-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanic acid
efaproxiral [vandf]
SCHEMBL1649963
CS-4950
BNFRJXLZYUTIII-UHFFFAOYSA-N
HY-13619
DTXSID40156934
NCGC00390260-01
2-(4-{2-[(3,5-dimethylphenyl)amino]-2-oxoethyl}phenoxy)-2-methylpropanoic acid
BCP21583
Q5347186
propanoic acid, 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-
F85273
MS-25216
EN300-18568053
2-(4-{[(3,5-dimethylphenyl)carbamoyl]methyl}phenoxy)-2-methylpropanoic acid

Research Excerpts

Overview

Efaproxiral (RSR13) is a synthetic allosteric modifier of haemoglobin. It acts by increasing the release of oxygen from Hb to the surrounding tissues.

ExcerptReferenceRelevance
"Efaproxiral (RSR 13) is an experimental synthetic allosteric modifier of haemoglobin (Hb) that acts by increasing the release of oxygen from Hb to the surrounding tissues. "( Detection of efaproxiral (RSR13) and its metabolites in equine by liquid chromatography tandem mass spectrometry.
Lam, G; Loganathan, D; Morrissey, B; Sandhu, J; Yi, R; Zhao, S, 2014)		2.21
"Efaproxiral (RSR13) is a synthetic allosteric modifier of haemoglobin that reduces its oxygen binding affinity. "( Efaproxiral: a novel radiation sensitiser.
Suh, JH, 2004)		3.21
"Efaproxiral is a synthetic allosteric modifier of hemoglobin that results in a shift of the hemoglobin oxygen dissociation curve to the right. "( Efaproxiral: a radiation enhancer used in brain metastases from breast cancer.
Charpentier, MM, 2005)		3.21

Pharmacokinetics

ExcerptReferenceRelevance
"To determine the safety, pharmacokinetics, and pharmacodynamic effect of 2-[4-(3, 5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylproprionic++ + acid (RSR13) 100 mg/kg/d with radiation therapy (RT) for glioblastoma multiforme (GBM)."( Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.
Engelhard, H; Gerber, M; Grossman, SA; Kleinberg, L; Lesser, G; Pearlman, J; Piantadosi, S; Ruffer, J, 1999)		0.3
" Pharmacokinetic (PK) and pharmacodynamic (PD) determinations were performed."( Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.
Engelhard, H; Gerber, M; Grossman, SA; Kleinberg, L; Lesser, G; Pearlman, J; Piantadosi, S; Ruffer, J, 1999)		0.3
" A Phase I open-label, multicenter dose and frequency escalation study was conducted to assess the safety, tolerance, pharmacokinetics, and pharmacodynamic effect of daily RSR13 administration to cancer patients receiving concurrent palliative radiotherapy (RT)."( A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.
Abraham, DJ; Dusenbery, KE; Gerber, MJ; Kavanagh, BD; Khandelwal, SR; Pearlman, AD; Roberts, JD; Schmidt-Ullrich, RK; Shaw, EG; Venitz, J, 2001)		0.31
" The pharmacodynamic effect of RSR13 on Hb-O(2) binding affinity was quantified by multipoint tonometry and expressed as an increase in p50, defined as the partial pressure of O(2) that results in 50% SaO(2)."( A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.
Abraham, DJ; Dusenbery, KE; Gerber, MJ; Kavanagh, BD; Khandelwal, SR; Pearlman, AD; Roberts, JD; Schmidt-Ullrich, RK; Shaw, EG; Venitz, J, 2001)		0.31
" Maximum pharmacodynamic effect occurred at the end of RSR13 infusion and was proportional to the RBC RSR13 concentration."( A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.
Abraham, DJ; Dusenbery, KE; Gerber, MJ; Kavanagh, BD; Khandelwal, SR; Pearlman, AD; Roberts, JD; Schmidt-Ullrich, RK; Shaw, EG; Venitz, J, 2001)		0.31
" The combined administration of RSR13 with 4 L/min supplemental O(2) yielded pharmacodynamic conditions in which hypoxic tumor radiosensitization can occur."( A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.
Abraham, DJ; Dusenbery, KE; Gerber, MJ; Kavanagh, BD; Khandelwal, SR; Pearlman, AD; Roberts, JD; Schmidt-Ullrich, RK; Shaw, EG; Venitz, J, 2001)		0.31

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51

Dosage Studied

ExcerptRelevanceReference
" A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO."( Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat.
Bart, RD; Grocott, HP; Pearlstein, RD; Sarraf-Yazdi, S; Sheng, H; Steffen, RP; Warner, DS, 1999)		0.3
"Grade 3 dose-limiting toxicity occurred in none of the patients with every-other-day dosing and in two of the 10 patients with daily dosing."( Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.
Engelhard, H; Gerber, M; Grossman, SA; Kleinberg, L; Lesser, G; Pearlman, J; Piantadosi, S; Ruffer, J, 1999)		0.3
" Phase I-III trial data have defined the safety profile and dosing of the drug, with the potential benefit for extended survival."( Efaproxiral: a novel radiation sensitiser.
Suh, JH, 2004)		1.77
" This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements."( Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases.
Craig, M; Hackman, J; May, J; Pintér, T; Shaw, E; Stea, B; Steffen, RP; Suh, JH, 2006)		2.07
" SMs allow prediction of clinical outcomes for different dosing regimens of drug candidates and patient individualization of treatment in clinical practice."( Using exposure-response and biomarkers to streamline early drug development.
Venitz, J, 2007)		0.34
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (29)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID233466The Hill coefficient at 50% saturation (n50) between 40 and 60% oxygen saturation (n50 control value with no effector present, 2.7).2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID226493Dose-response study in whole blood at a concentration of 1.0 mM1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID233365Hill coefficient at 50% saturation in the presence of effector2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID221814Ability to right-shift the oxygen equilibrium curves (OECs) quantified by ability to increase in P50 in whole blood analyses.2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID226495Dose-response study in whole blood at a concentration of 2.0 mM1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID1846360Induction of glucose-stimulated insulin secretion in rat INS-1 832/13 cells incubated for 5 mins by ELISA assay2021Bioorganic & medicinal chemistry letters, 06-01, Volume: 41FFAR1/GPR40: One target, different binding sites, many agonists, no drugs, but a continuous and unprofitable tug-of-war between ligand lipophilicity, activity, and toxicity.
AID226498Ratio of P50e to P50c (P50 control value with no effector present, 5 mmHg)2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID223083P50C is the control value in whole blood in experiment.2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID226489Oxygen pressure in mmHg at which the control hemoglobin solution (no compound) was 50% saturated with oxygen.1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID226496Dose-response study in whole blood at a concentration of 4.0 mM1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID226490Oxygen pressure in mmHg at which the control hemoglobin solution (in presence of 10 mM compound) was 50% saturated with oxygen.1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID233467The Hill coefficient at 50% saturation (n50) in the presence of effector.2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID221815Ability to right-shift the oxygen equilibrium curves (OECs) quantified by ability to increase in P50 at which Hb was 50% saturated with oxygen in the absence of the effector.2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID221817Ability to right-shift the oxygen equilibrium curves (OECs) quantified by ability to increase in P50 at which Hb was 50% saturated with oxygen in the presence of the effector at the concentration of 5 mM.2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID223085P50e is the value in the presence of the effector in whole blood in experiment 2 (in vitro)2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID223084P50e is the value in the presence of the effector in whole blood in experiment 1 (in vitro)2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID221148Oxygen pressure at which hemoglobin is 50% saturated with oxygen in the presence of the effector.2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID226494Dose-response study in whole blood at a concentration of 10.0 mM1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
AID226497Ratio of P50 of the control / P50 of the effector (P50 control value with no effector present 5.0 mmHg, in case of DMSO is 4.7 mmHg )2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID221819The difference in the partial pressure of oxygen at 50% saturated Hb2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID226488The difference between P50e and P50c tested. 2000Journal of medicinal chemistry, Dec-14, Volume: 43, Issue:25
Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin.
AID221818Oxygen pressure in mmHg at which Hb is 50% saturated with oxygen at 50-60 uM heme concentration and in the presence of 0.5 mM effector.2002Journal of medicinal chemistry, Mar-14, Volume: 45, Issue:6
Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin.
AID226492Dose-response study in whole blood at a concentration of 0.5 mM1991Journal of medicinal chemistry, Feb, Volume: 34, Issue:2
Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (76)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's23 (30.26)18.2507
2000's43 (56.58)29.6817
2010's4 (5.26)24.3611
2020's6 (7.89)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.84

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.84 (24.57)
Research Supply Index4.50 (2.92)
Research Growth Index4.55 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.84)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials13 (17.11%)5.53%
Reviews7 (9.21%)6.00%
Case Studies1 (1.32%)4.05%
Observational0 (0.00%)0.25%
Other55 (72.37%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (5)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma [NCT00005855]Phase 1/Phase 248 participants (Anticipated)Interventional2000-07-31Completed
A Phase III, Randomized, Open-Label, Comparative Study of Standard Whole Brain Radiation Therapy With or Without RSR13 in Patients With Brain Metastases [NCT00005887]Phase 30 participants Interventional2000-02-29Completed
A Phase III Randomized, Open-Label Comparative Study of Induction Chemotherapy Followed by Thoracic Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Patients With Locally Advanced Unresectable (Stage IIIA/IIIB [NCT00055887]Phase 30 participants (Actual)Interventional2002-11-30Withdrawn(stopped due to Study never started. No patients were enrolled.)
A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Women With Brain Metastases From Breast Cancer [NCT00083304]Phase 3368 participants (Actual)Interventional2004-02-29Completed
A Phase II Study of Induction Chemotherapy With Paclitaxel and Carboplatin Followed by Radiation Therapy With RSR13 for Locally Advanced Inoperable Non-Small Cell Lung Cancer [NCT00004202]Phase 20 participants Interventional1998-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
lactic acid
Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed). 2-hydroxypropanoic acid : A 2-hydroxy monocarboxylic acid that is propanoic acid in which one of the alpha-hydrogens is replaced by a hydroxy group.		2.41202-hydroxy monocarboxylic acidalgal metabolite;
Daphnia magna metabolite
phytic acid
Phytic Acid: Complexing agent for removal of traces of heavy metal ions. It acts also as a hypocalcemic agent.. myo-inositol hexakisphosphate : A myo-inositol hexakisphosphate in which each hydroxy group of myo-inositol is monophosphorylated.		2.0210inositol phosphate
clofibrate
angiokapsul: contains clofibrate & insoitolnicotinate		1.9910aromatic ether;
ethyl ester;
monochlorobenzenes		anticholesteremic drug;
antilipemic drug;
geroprotector;
PPARalpha agonist
furosemide
Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.. furosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.		210chlorobenzoic acid;
furans;
sulfonamide		environmental contaminant;
loop diuretic;
xenobiotic
phenyl acetate
phenyl acetate: The ester formed between phenol and acetic acid. Don't confuse with phenylacetic acid derivatives listed under PHENYLACETATES.. phenyl acetate : An acetate ester obtained by the formal condensation of phenol with acetic acid.		210benzenes;
phenyl acetates
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		4.3211taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
bezafibrate
[no description available]		3.8530aromatic ether;
monocarboxylic acid amide;
monocarboxylic acid;
monochlorobenzenes		antilipemic drug;
environmental contaminant;
geroprotector;
xenobiotic
thiophenoxyacetic acid
thiophenoxyacetic acid: structure		3.4110
carbogen
carbogen: mixture of 95% O2 & 5% CO2		210
sr141716
[no description available]		2.0410amidopiperidine;
carbohydrazide;
dichlorobenzene;
monochlorobenzenes;
pyrazoles		anti-obesity agent;
appetite depressant;
CB1 receptor antagonist
l 345
L 345: RN & structure given in first source		1.9710
rsr 4
4-(2-(4-(((3,5-dichloroanilino)carbonyl)methyl)phenoxy)-2-methylpropionic acid): allosteric effector of hemoglobin; structure given in first source		2.6730
agn 190299
AGN 190299: a metabolite of the synthetic retinoid AGN 190168; structure given in first source. tazarotenic acid : A thiochromane that is acetylene in which the hydrogens are replaced by 5-carboxypyridin-2-yl and 4,4-dimethylthiochroman-6-yl groups. It is the active form of the prodrug tazarotene.		3.4110monocarboxylic acid;
pyridines;
retinoid;
thiochromane		keratolytic drug;
teratogenic agent
lonafarnib
lonafarnib: inhibitor of farnesyl protein transferase. lonafarnib : A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase inhibitor.		2.02104-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamideantineoplastic agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor
hydroxyl radical
Hydroxyl Radical: The univalent radical OH. Hydroxyl radical is a potent oxidizing agent.		210oxygen hydride;
oxygen radical;
reactive oxygen species
l 35
L 35: a negative effector of hemoglobin; RN & structure given in first source		1.9710
carboplatin
[no description available]		10.0231
bradykinin
[no description available]		2.0210oligopeptidehuman blood serum metabolite;
vasodilator agent
lr 16
LR 16: structure given in first source; has potent effects on oxygen affinity of hemoglobin, on blood cholesterol and on low density lipoprotein		1.9710
4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid: A non-penetrating amino reagent (commonly called SITS) which acts as an inhibitor of anion transport in erythrocytes and other cells.		1.9810stilbenoid
aluminum
Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98.		2.0410boron group element atom;
elemental aluminium;
metal atom
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid: An inhibitor of anion conductance including band 3-mediated anion transport.		1.9810
dizocilpine maleate
Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.. dizocilpine maleate : A maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid.		2.420maleate salt;
tetracyclic antidepressant		anaesthetic;
anticonvulsant;
neuroprotective agent;
nicotinic antagonist;
NMDA receptor antagonist
phosphocreatine
Phosphocreatine: An endogenous substance found mainly in skeletal muscle of vertebrates. It has been tried in the treatment of cardiac disorders and has been added to cardioplegic solutions. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1996). phosphagen : Any of a group of guanidine or amidine phosphates that function as storage depots for high-energy phosphate in muscle with the purpose of regenerating ATP from ADP during muscular contraction.. N-phosphocreatine : A phosphoamino acid consisting of creatine having a phospho group attached at the primary nitrogen of the guanidino group.		3.821phosphagen;
phosphoamino acid		human metabolite;
mouse metabolite
motexafin gadolinium
[no description available]		3.1310
aq4n
AQ4N: structure given in first source		3.1310
icatibant
icatibant: a potent bradykinin (B2) receptor antagonist; WIN 65365 is an L-Tic(7) stereoisomer. icatibant : A ten-membered synthetic oligopeptide consisting of D-Arg, Arg, Pro, Hyp, Gly, Thi, Ser, D-Tic, Oic, and Arg residues joined in sequrence. A bradykinin receptor antagonist used as its acetate salt for the treatment of acute attacks of hereditary angioedema in adult patients.		2.0210
tak-875
[no description available]		3.4110biphenyls
piperidines
Piperidines: A family of hexahydropyridines.		2.4420
heme
Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.. ferroheme : Any iron(II)--porphyrin coordination complex.. ferroheme b : Heme b in which the iron has oxidation state +2.. heme : A heme is any tetrapyrrolic chelate of iron.		1.9810
tirapazamine
Tirapazamine: A triazine derivative that introduces breaks into DNA strands in hypoxic cells, sensitizing tumor cells to the cytotoxic activity of other drugs and radiation.. tirapazamine : A member of the class of benzotriazines that is 1,2,4-benzotriazine carrying an amino substituent at position 3 and two oxido substituents at positions 1 and 4.		3.1310aromatic amine;
benzotriazines;
N-oxide		antibacterial agent;
antineoplastic agent;
apoptosis inducer
ConditionIndicatedRelationship StrengthStudiesTrials
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		04.7871
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Hyperoxia
An abnormal increase in the amount of oxygen in the tissues and organs.		02.610
Peripheral Arterial Diseases
[description not available]		02.1510
Muscle Contraction
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.		02.1510
Peripheral Arterial Disease
Lack of perfusion in the EXTREMITIES resulting from atherosclerosis. It is characterized by INTERMITTENT CLAUDICATION, and an ANKLE BRACHIAL INDEX of 0.9 or less.		02.1510
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		04.1131
Cardiac Failure
[description not available]		02.0410
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		02.0410
Astrocytoma, Grade IV
[description not available]		04.3522
Benign Supratentorial Neoplasms
[description not available]		03.3911
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		04.3522
Acute Hemolytic Transfusion Reaction
[description not available]		02.0110
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		02.0110
Transfusion Reaction
Complications of BLOOD TRANSFUSION. Included adverse reactions are common allergic and febrile reactions; hemolytic (delayed and acute) reactions; and other non-hemolytic adverse reactions such as infections and adverse immune reactions related to immunocompatibility.		02.0110
Benign Neoplasms, Brain
[description not available]		09.29127
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		09.29127
Benign Neoplasms
[description not available]		06.0241
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		18.0241
Apoplexy
[description not available]		02.0110
Cerebral Ischemia
[description not available]		02.9140
Brain Ischemia
Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.		02.9140
Stroke
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)		02.0110
Hemorrhagic Shock
[description not available]		02.0110
Experimental Mammary Neoplasms
[description not available]		02.6930
Cancer, Radiation-Induced
[description not available]		02.0210
Fibrosarcoma
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)		02.4120
Carcinoma, Non-Small Cell Lung
[description not available]		06.4133
Cancer of Lung
[description not available]		06.2742
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		06.4133
Lung Neoplasms
Tumors or cancer of the LUNG.		18.2742
Arteriosclerosis, Coronary
[description not available]		03.4111
Heart Disease, Ischemic
[description not available]		04.4851
Coronary Artery Disease
Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.		03.4111
Myocardial Ischemia
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).		04.4851
Breast Cancer
[description not available]		07.8863
Breast Neoplasms
Tumors or cancer of the human BREAST.		19.8863
Animal Mammary Carcinoma
[description not available]		02.0310
Hyperventilation
A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide.		02.0210
Anesthesia
A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.		02.4120
Cancer of Skin
[description not available]		02.0310
Skin Neoplasms
Tumors or cancer of the SKIN.		02.0310
Anterior Choroidal Artery Infarction
[description not available]		02.6930
Brain Vascular Disorders
[description not available]		01.9910
Cerebral Infarction
The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).		02.6930
Cerebrovascular Disorders
A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.		01.9910
Acute Brain Injuries
[description not available]		02.420
Brain Hemorrhage, Cerebral
[description not available]		01.9910
Hematoma, Subdural
Accumulation of blood in the SUBDURAL SPACE between the DURA MATER and the arachnoidal layer of the MENINGES. This condition primarily occurs over the surface of a CEREBRAL HEMISPHERE, but may develop in the spinal canal (HEMATOMA, SUBDURAL, SPINAL). Subdural hematoma can be classified as the acute or the chronic form, with immediate or delayed symptom onset, respectively. Symptoms may include loss of consciousness, severe HEADACHE, and deteriorating mental status.		02.420
Brain Injuries
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.		02.420
Cerebral Hemorrhage
Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.		01.9910
Ischemia
A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.		01.9910
Hibernation, Myocardial
[description not available]		02.420
Carcinoma, Lewis Lung
A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.		01.9910
Injury, Ischemia-Reperfusion
[description not available]		01.9910
Reperfusion Injury
Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.		01.9910
Carcinoma, Epidermoid
[description not available]		0210
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		0210
Anoxemia
[description not available]		0210
Hypoxia
Sub-optimal OXYGEN levels in the ambient air of living organisms.		0210
Anterior Circulation Transient Ischemic Attack
[description not available]		02.6930
Ischemic Attack, Transient
Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6)		02.6930
Cerebral Infarction, Middle Cerebral Artery
[description not available]		0210
Infarction, Middle Cerebral Artery
NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction.		0210
Carcinoma, Large Cell
A tumor of undifferentiated (anaplastic) cells of large size. It is usually bronchogenic. (From Dorland, 27th ed)		0210
Acute Kidney Failure
[description not available]		0210
Acute Kidney Injury
Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.		0210
Anemia
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.		02.0110