Page last updated: 2024-12-06

clodronic acid

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Description

clondronate(2-) : The dianion resulting from the removal of two protons from clondronic acid. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

clodronic acid : An organochlorine compound that is methylene chloride in which both hydrogens are replaced by phosphonic acid groups. It inhibits bone resorption and soft tissue calcification, and is used (often as the disodium salt tetrahydrate) as an adjunct in the treatment of severe hypercalcaemia associated with malignancy, and in the management of osteolytic lesions and bone pain associated with skeletal metastases. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID4668904
CHEBI ID59585
MeSH IDM0006270
PubMed CID25419
CHEMBL ID12318
CHEBI ID110423
SCHEMBL ID18982
MeSH IDM0006270

Synonyms (88)

Synonym
dichloromethylenebisphosphonate
NCGC00162143-01
NCGC00162143-02
dichloromethylene-1,1-bis(hydrogen phosphate)
CHEBI:59585
clondronate(2-)
(dichloromethanediyl)bis[hydrogen (phosphonate)]
clodronate dianion
[dichloro-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate
CCG-204491
STL335521
AKOS022142158
NCGC00162143-03
AB01566923_01
Q27126791
NCGC00162143-08
acidum clodronicum [inn-latin]
phosphonic acid, (dichloromethylene)di-
phosphonic acid, (dichloromethylene)bis-
methanedichlorodiphosphonic acid
dichloromethanediphosphonic acid
einecs 234-212-1
brn 1876367
acido clodronico [inn-spanish]
acide clodronique [inn-french]
LOPAC0_000398
HSCI1_000244
clodronic acid (usan/inn)
D03545
10596-23-3
methanedichlorodiphosphonate
[dichloro(phosphono)methyl]phosphonic acid
clodronate
(dichloromethylene)bisphosphonic acid
dichloromethylidene diphosphonate
clodronic acid
(dichloromethylene)diphosphonic acid
DB00720
dichloromethylene-1,1-bisphosphonic acid
dichloromethylene-1,1-diphosphonic acid
(dichloro-phosphono-methyl)-phosphonic acid
(lip-c)
(dichloromethanediyl)bis(phosphonic acid)
liposomes containing clodronic acid
acide clodronique
acidum clodronicum
CHEBI:110423 ,
clodronsaeure
acido clodronico
HMS2089N14
CHEMBL12318 ,
bisphosphonate clodronate
bdbm50216172
dichlormethylen-bis(phosphonsaeure)
0813bz6866 ,
unii-0813bz6866
clodronic acid [usan:inn:ban]
AKOS016013957
FT-0603207
clodronic acid [who-dd]
clodronic acid [green book]
clodronic acid [inn]
clodronic acid [mart.]
clodronic acid [usan]
clodronic acid [mi]
BRD-K72542090-236-01-0
SCHEMBL18982
AB01275478-01
DTXSID8046959
dichloromethylenediphosphonic acid
dichloromethylene bisphosphonic acid
dichloromethylenebisphosphonic acid
ACSIXWWBWUQEHA-UHFFFAOYSA-N
ch4cl2o6p2
gtpl9605
(dichloro-phosphonomethyl)phosphonic acid
dichloromethylene diphosphonic acid
(dichloromethylene)bis(phosphonic acid)
mfcd00867075
Q2341200
2-o-tolylaminopropionicacid
AMY15534
clodronic-acid
H11492
SY047909
A922145
HY-B0657
CS-0009576

Research Excerpts

Overview

Clodronic acid is a non-nitrogen-containing bisphosphonate. It is used in the prevention and treatment of postmenopausal and secondary osteoporosis.

ExcerptReferenceRelevance
"Clodronic acid is a non-nitrogen-containing bisphosphonate largely used from some decades in the prevention and treatment of postmenopausal and secondary osteoporosis. "( Clodronate in the management of different musculoskeletal conditions.
Bianchi, G; Cantarini, L; Dalle Carbonare, L; Frediani, B; Giusti, A; Malavolta, N; Molfetta, L; Saviola, G, 2018
)
1.92
"Clodronic acid is a bisphosphonate used in the prevention and treatment of postmenopausal bone loss. "( Effects of two administration schemes of intramuscular clodronic acid on bone mineral density: a randomized, open-label, parallel-group study.
Frediani, B, 2011
)
2.06
"Clodronic acid is a non-aminate bisphosphonate capable of inhibiting bone resorption. "( [Use of clodronic acid in mineral metabolism conditions: state of the art in 2000].
Brandi, ML, 2001
)
2.19

Effects

ExcerptReferenceRelevance
"Clodronic acid has been shown to be effective in the maintenance or improvement of bone mineral density when given orally, intramuscularly or intravenously in patients with osteoporosis."( Clodronic acid formulations available in Europe and their use in osteoporosis: a review.
Cavalieri, L; Cremonesi, G; Frediani, B, 2009
)
2.52

Toxicity

ExcerptReferenceRelevance
"Research into the pathogenesis of acetaminophen (paracetamol)-induced hepatotoxicity has concentrated on the generation of toxic metabolites by the hepatocytes."( Role of macrophages in acetaminophen (paracetamol)-induced hepatotoxicity.
Breach, CS; Brown, IN; Goldin, RD; Ratnayaka, ID; Wickramasinghe, SN, 1996
)
0.29
" The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease."( Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.
Kozel, TR; Lupan, DM; Manalo, PB; Roberts, JS; Savoy, AC; Schlageter, AM; Weinhold, LC, 1997
)
0.3
" Adverse events (AEs) and laboratory parameters were followed up regularly for the total study period."( Extended safety profile of oral clodronate after long-term use in primary breast cancer patients.
Atula, S; Kanis, J; McCloskey, E; Nevalainen, J; Paterson, A; Powles, T, 2003
)
0.32
" This study shows that subcutaneous clodronate is safe and can lower serum calcium levels in malignant hypercalcemia."( Safety of subcutaneous clodronate and efficacy in hypercalcemia of malignancy: a novel route of administration.
Hanson, J; Neumann, C; Quan, HK; Roemer-Bécuwe, C; Romano, F; Vigano, A; Walker, P, 2003
)
0.32
" Our current study suggests that adjuvant tamoxifen therapy reverses the adverse effects of chemotherapy-induced ovarian failure on total and LDL cholesterol and even lowers their serum levels below the baseline."( Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids.
Blomqvist, C; Elomaa, I; Saarto, T; Taskinen, MR; Vehmanen, L, 2004
)
0.32
"Many efforts have been made to obtain active and less toxic Vitamin D analogs for new clinical applications."( Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191).
Dzimira, S; Kuśnierczyk, H; Kutner, A; Madej, J; Opolski, A; Pełczyńska, M; Szelejewski, W; Wietrzyk, J, 2004
)
0.32
" The nitrogen-containing bisphosphonate pamidronate was significantly more toxic on a panel of eight neuroblastoma cell lines than the non-nitrogen-containing bisphosphonates, clodronate and tiludronate."( In vitro toxicity of bisphosphonates on human neuroblastoma cell lines.
Boos, J; Lanvers-Kaminsky, C; Vorotnjak, M, 2004
)
0.32
" The safety was assessed based on the frequencies of the reported adverse effects as nausea, vomiting, anemia, etc."( Zoledronic acid and clodronate in the treatment of malignant bone metastases with hypercalcaemia; efficacy and safety comparative study.
Habib, EE; Sabry, NA, 2011
)
0.37
" The incidence of renal adverse events was similar for ZOL and CLO."( Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results.
Ashcroft, AJ; Bell, SE; Boyd, KD; Byrne, J; Child, JA; Cook, G; Davies, FE; Drayson, MT; Feyler, S; Gregory, WM; Jackson, GH; Morgan, GJ; Navarro Coy, N; Osborne, WL; Owen, RG; Roddie, H; Ross, FM; Rudin, C; Szubert, AJ; Wu, P, 2014
)
0.4

Pharmacokinetics

ExcerptReferenceRelevance
" On the basis of urinary excretion data, there was a slow terminal elimination phase with a half-life of 12."( Pharmacokinetics of clodronate in patients with metastatic breast cancer.
Elomaa, I; Kärkkäinen, S; Nurmi, AK; Pentikäinen, PJ, 1989
)
0.28
"The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency."( Pharmacokinetics of clodronate in renal failure.
Castren-Kortekangas, P; Juhakoski, A; Ojanen, S; Pasternack, A; Saha, H; Tokola, O; Tuominen, J, 1994
)
0.29
" We conducted a randomized, two-period cross-over pharmacokinetic (phase I) study to assess the relative bioavailability of two different clodronate preparations: an 800 mg tablet and a 400 mg capsule."( Pooling of clodronate urinary excretion data: a new pharmacokinetic method to study drugs with highly variable gastrointestinal absorption.
Castrén-Kortekangas, P; Juhakoski, A; Laitinen, K; Liukko-Sipi, S; Löyttyniemi, E; Smal, J, 1997
)
0.3
"A single intravenous dose pharmacokinetic study."( Pharmacokinetics of clodronate in peritoneal dialysis patients.
Ala-Houhala, IO; Liukko-Sipi, SH; Pasternack, AI; Saha, HH; Ylitalo, P,
)
0.13
"The pharmacokinetic parameters describing the fate of an intravenous infusion of 300 mg clodronate disodium were studied in 10 haemodialysis patients."( Pharmacokinetics of clodronate in haemodialysis patients.
Ala-Houhala, I; Liukko-Sipi, S; Pasternack, A; Saha, H; Ylitalo, P, 1999
)
0.3
" Pharmacokinetic parameters were calculated with a three-compartmental model."( Comparison of pharmacokinetics of clodronate after single and repeated doses.
Elo, HA; Holli, K; Juhakoski, A; Liukko-Sipi, S; Mönkkönen, J; Ylitalo, P; Ylitalo, R, 1999
)
0.3
" The method was accurate and reproducible, and was successfully applied to determine the pharmacokinetic parameters of clodronate in healthy volunteers after intravenous infusion and intramuscular injection of 200 mg of the compound."( Determination of disodium clodronate in human plasma and urine using gas-chromatography-nitrogen-phosphorous detections: validation and application in pharmacokinetic study.
Barbera, S; Canaparo, R; Casale, F; Della Pepa, C; Eandi, M; Muntoni, E; Romano, P; Serpe, L; Zara, GP, 2004
)
0.32
" The area under the 24-h concentration-time curve (AUC0-24) enlarged and the elimination half-life (t1/2elim) prolonged progressively when the renal function was impaired."( Steady state pharmacokinetics and dose equivalents of oral clodronate in renal failure.
Ala-Houhala, I; Liukko-Sipi, S; Mäkelä, S; Saha, H; Ylitalo, P, 2011
)
0.37
" Drug concentrations were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis was performed."( Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.
Knych, HK; Krueger, CR; Leise, BS; Mitchell, CF, 2020
)
0.56
" Here, we show that highly cytotoxic doxorubicin- or clodronate-loaded liposomes, which are widely used for cancer therapy and biomedical research, induce a similar increase in the nanoparticle blood circulation half-life in mice as the MPS-cytoblockade, which only gently and temporarily saturates the macrophages with the organism's own erythrocytes."( Comparative Study of Nanoparticle Blood Circulation after Forced Clearance of Own Erythrocytes (Mononuclear Phagocyte System-Cytoblockade) or Administration of Cytotoxic Doxorubicin- or Clodronate-Loaded Liposomes.
Egorova, EA; Khabibullina, NF; Komarova, KS; Mochalova, EN; Nikitin, MP; Nikitin, PI; Shipunova, VO, 2023
)
0.91
"11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study."( Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses.
Bradbery, AN; Colbath, AC; Kottwitz, JJ; Leatherwood, JL; Nielsen, BD; Panek, CL; Paris, BL; Robison, CI; Vergara-Hernandez, FB; Welsh, TH, 2023
)
0.91
"The pharmacokinetic parameters and PPB of CLO in juvenile sheep were similar to those previously reported in horses."( Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses.
Bradbery, AN; Colbath, AC; Kottwitz, JJ; Leatherwood, JL; Nielsen, BD; Panek, CL; Paris, BL; Robison, CI; Vergara-Hernandez, FB; Welsh, TH, 2023
)
0.91

Compound-Compound Interactions

ExcerptReferenceRelevance
" The aim of this study is to evaluate the efficacy of a non-aminobiphosphonate combined with a surfactant to increase the ability of the drug to link to the implant and bone surfaces in the development of osseointegration in rabbits."( Clodronate combined with a surfactant (Tween 20) does not improve osseointegration: a rabbit immunohistomorphometric study.
Berardi, D; Paolantonio, M; Perfetti, G; Raffaelli, L; Trisi, P,
)
0.13
"The purpose of this study was to investigate the effect of liposomal clodronate combined with Cisplatin or Sorafenib on the FOXQ1 expression and biological function of hepatocellular carcinoma cell lines."( Liposomal clodronate combined with Cisplatin or Sorafenib inhibits hepatocellular carcinoma cell proliferation, migration and invasion by suppressing FOXQ1 expression.
Chen, Y; Ma, C; Shao, B; Zhang, F; Zhou, Y, 2020
)
0.56
" We found that DOX-LIP combined with CL-LIP could effectively inhibit the occurrence and development of liver cancer without major organ damage and side effects."( Doxorubicin-liposome combined with clodronate-liposome inhibits hepatocellular carcinoma through the depletion of macrophages and tumor cells.
Han, Z; Hou, X; Lu, Y; Sheng, D; Sun, G; Wang, X; Wei, L; Yang, X; Zhang, H; Zhang, L, 2022
)
0.72

Bioavailability

ExcerptReferenceRelevance
" The QSAR studies show the importance of the steric properties of these new bisphosphonate derivatives for the inhibition of bone resorption in bone cell cultures and for their bioavailability in rats."( Comparative molecular field analysis of some clodronic acid esters.
Björkroth, JP; Hanhijärvi, H; Hannuniemi, R; Juhakoski, A; Kippo, K; Kleimola, T; Laurén, L; Lindroos, J; Pakkanen, TA; Pohjala, E, 1991
)
0.54
"Bisphosphonates are poorly absorbed when given orally and their absorption is subject to a large inter- and intraindividual variability."( Sodium EDTA enhances intestinal absorption of two bisphosphonates.
Fleisch, H; Janner, M; Mühlbauer, RC, 1991
)
0.28
" Cl2MDP is poorly absorbed with an absolute bioavailability of only 1% to 2%."( Clodronate kinetics and bioavailability.
Ampulski, RS; Benedict, JJ; Floyd, BF; Poynor, WJ; Slough, CL; Talbert, RL; Yakatan, GJ, 1982
)
0.26
" Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases."( Effect of concomitant administration of clodronate and estramustine phosphate on their bioavailability in patients with metastasized prostate cancer.
Castrén-Kortekangas, P; Kylmälä, T; Seppänen, J; Tammela, TL; Ylitalo, P, 1996
)
0.29
" We conducted a randomized, two-period cross-over pharmacokinetic (phase I) study to assess the relative bioavailability of two different clodronate preparations: an 800 mg tablet and a 400 mg capsule."( Pooling of clodronate urinary excretion data: a new pharmacokinetic method to study drugs with highly variable gastrointestinal absorption.
Castrén-Kortekangas, P; Juhakoski, A; Laitinen, K; Liukko-Sipi, S; Löyttyniemi, E; Smal, J, 1997
)
0.3
" In conclusion, these novel dianhydride derivatives may be potentially useful prodrugs of clodronate which, due to their lipophilicity and lack of Ca2+ chelating, increase its bioavailability after oral administration."( Bisphosphonate prodrugs: synthesis and in vitro evaluation of novel clodronic acid dianhydrides as bioreversible prodrugs of clodronate.
Ahlmark, M; Järvinen, T; Niemi, R; Taipale, H; Vepsäläinen, J, 1999
)
0.54
" Although newer bisphosphonates are more potent, oral bioavailability remains < 1%."( Oral bisphosphonates: A review of clinical use in patients with bone metastases.
Berenson, J; Hortobagyi, G; Lipton, A; Major, PP, 2000
)
0.31
" Low oral bioavailability is the most likely reason for this difference."( Oral bisphosphonates: A review of clinical use in patients with bone metastases.
Berenson, J; Hortobagyi, G; Lipton, A; Major, PP, 2000
)
0.31
"Because of the low and variable bioavailability of bisphosphonates and the huge effect of food on their gastrointestinal absorption, it is of utmost importance to know the optimal timing of drug intake in relation to food intake."( Timing of food intake has a marked effect on the bioavailability of clodronate.
Harju, P; Kleimola, T; Laitinen, K; Löyttyniemi, E; Patronen, A; Perttunen, K; Pylkkänen, L, 2000
)
0.31
"Clodronate, like other bisphosphonates, is poorly absorbed from the gastrointestinal tract, mainly due to its high hydrophilicity and ability to form complexes with divalent cations in the gastrointestinal tract."( Effects of calcium and lipophilicity on transport of clodronate and its esters through Caco-2 cells.
Järvinen, T; Mönkkönen, J; Niemi, R; Raiman, J; Vepsäläinen, J; Yritys, K, 2001
)
0.31
" Clodronate has been administered orally in most clinical studies so far despite of its poor bioavailability from the gastrointestinal tract."( Bone mineral density in multiple myeloma patients after intravenous clodronate therapy.
Adam, Z; Dusek, L; Hájek, R; Prokes, B; Tomíska, M; Vorlícek, J, 2001
)
0.31
" The oral bioavailability of BPs is ca."( Bisphosphonate prodrugs.
Vepsäläinen, JJ, 2002
)
0.31
" The purpose of this study was to examine the absolute bioavailability of clodronate from two different oral doses."( The absolute bioavailability of clodronate from two different oral doses.
Ikävalko, H; Perttunen, K; Pylkkänen, L; Rosnell, J; Vaho, H; Villikka, K, 2002
)
0.31
" One obstacle to the routine use of bisphosphonates in palliative patients is that oral bisphosphonates have low bioavailability and a degree of gastrointestinal toxicity that may explain poor compliance."( Safety of subcutaneous clodronate and efficacy in hypercalcemia of malignancy: a novel route of administration.
Hanson, J; Neumann, C; Quan, HK; Roemer-Bécuwe, C; Romano, F; Vigano, A; Walker, P, 2003
)
0.32
" Problems with the study populations, drug bioavailability and potency, statistical power and end point definition may have contributed to the negative results of these other studies."( Bisphosphonates to prevent skeletal complications in men with metastatic prostate cancer.
Smith, MR, 2003
)
0.32
"Although substances, which can increase the paracellular permeability of intestinal mucosa, could be very helpful for increasing the bioavailability of hydrophilic drugs, they are not used therapeutically due to the possibilities of acute or long-term toxicity (intestinal inflammations due to penetration of bacterial fragments into subepithelial spaces)."( The effect of clodronate on the integrity and viability of rat small intestine in vitro-a comparison with EDTA.
Kristl, A; Vadnjal, L; Zakelj, S, 2005
)
0.33
" Due to its high polarity it has a low and highly variable oral bioavailability which results in low plasma concentrations and requires sensitive bioanalytical methods to characterize its pharmacokinetics in human."( LC-MS/MS method for the determination of clodronate in human plasma.
Hasan, M; Oswald, S; Schumacher, G; Seekamp, A; Siegmund, W; Taedken, T, 2014
)
0.4
" This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies."( Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.
Al-Nawas, B; Jung, J; Kwon, YD; Pabst, AM; Park, JS; Righesso, L; Walter, C, 2018
)
0.48
" These results meant that the removal of macrophages would decrease the nanoparticles accumulation in the liver and better the biodistribution and bioavailability of nanoparticles delivery systems."( Temporary suppression the sequestrated function of host macrophages for better nanoparticles tumor delivery.
Han, T; Hao, J; Liu, J; Tang, H; Wang, M; Wang, X; Wang, Y; Zhuang, Q, 2018
)
0.48
" For clinical use, clodronate was developed in oral and injectable formulations; while poorly absorbed from the gastro-intestinal tract, its absorption at 1-3% of the administered dose is approximately three-fold higher than for nitrogen-containing bisphosphonates."( Clodronate.
Kanis, JA; McCloskey, E; Paterson, AH; Powles, T, 2021
)
0.62

Dosage Studied

ExcerptRelevanceReference
" The author discusses the administration, dosage and side effects, and results of current studies."( Bisphosphonate treatment of bone metastases and hypercalcemia of malignancy.
Coleman, RE, 1991
)
0.28
" No clear differences in concentration of clodronate in bone could be seen after different dosage schedules when the total doses were the same."( Level of clodronate in bone after single and repeated subcutaneous injections in rats.
Laurén, L; Osterman, T, 1991
)
0.28
" The initial dosage was 300 mg intravenously daily."( Treatment of tumor hypercalcemia with clodronate.
Scharla, SH; Ziegler, R, 1989
)
0.28
" The serum concentrations-time curve over the first 8 hr after intravenous dosing appears biexponential with the disposition phase having a harmonic mean half-life (t 1/2) of 2 hr."( Clodronate kinetics and bioavailability.
Ampulski, RS; Benedict, JJ; Floyd, BF; Poynor, WJ; Slough, CL; Talbert, RL; Yakatan, GJ, 1982
)
0.26
"Application of ion chromatography (IC) to the analysis of non-chromophoric bisphosphonate drugs in pharmaceutical dosage formulations is described."( Determination of bisphosphonate drugs in pharmaceutical dosage formulations by ion chromatography with indirect UV detection.
Bell, C; Brooks, MA; Chamberlin, SD; Forsyth, RJ; Ip, DP; Tsai, EW, 1994
)
0.29
" The aim of the study was to derive data for adjustment of dosage in relation to renal function."( Pharmacokinetics of clodronate in renal failure.
Castren-Kortekangas, P; Juhakoski, A; Ojanen, S; Pasternack, A; Saha, H; Tokola, O; Tuominen, J, 1994
)
0.29
" However, intratracheal inoculation of liposomes containing dichloro-methylene-diphosphonate at a dosage shown to eliminate the majority of resident alveolar macrophages (AM) rapidly restores the immunocompetence of these lung T-cell populations."( Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages.
Holt, PG; Kees, UR; Kraal, G; Strickland, DH; Thepen, T, 1993
)
0.29
" Two days later, the animals were challenged intraperitoneally with zymosan suspended in paraffin to determine a dose-response curve (0."( Macrophage elimination increases bacterial translocation and gut-origin septicemia but attenuates symptoms and mortality rate in a model of systemic inflammation.
Berg, RD; Deitch, EA; Goris, RJ; Haskel, Y; Lu, Q; Nieuwenhuijzen, GA; van Rooijen, N, 1993
)
0.29
" Dosage could not be shown to influence the inhibition of tumor osteolysis in the long-term bone protective treatment."( Prophylactic treatment of skeletal metastases, tumor-induced osteolysis, and hypercalcemia in rats with the bisphosphonate Cl2MBP.
Krempien, B; Manegold, C, 1993
)
0.29
" The present data together with information provided by previous studies suggest that 300 mg of clodronate given as an 2-h infusion immediately prior to haemodialysis is an adequate dosage for ESRD patients."( Removal of clodronate by haemodialysis in end-stage renal disease patients.
Beigel, AE; Olbricht, CJ; Rienhoff, E, 1995
)
0.29
"The effects of slow-release calcium clodronate on rat adjuvant arthritis were investigated using two different dosing schedules."( Slow-release clodronate in prevention of inflammation and bone loss associated with adjuvant arthritis.
Hannuniemi, R; Kippo, K; Laurén, L; Osterman, T; Pasanen, I; Sellman, R; Väänänen, K; Virtamo, T, 1997
)
0.3
" Older and newer-generation bisphosphonates have an inhibitory effect on calcium oxalate urolithiasis that is demonstrable at relatively infrequent dosing intervals in vivo."( Inhibition of calcium oxalate urolithiasis in a rat model of lithogenesis using bisphosphonates.
Gupta, M; Smith, AD; Tuncay, OL; Valderrama, E, 1997
)
0.3
" Following treatment with clodronate-containing liposomes, macrophages were killed in a dose-response fashion over a range of 5-200 microliters liposomes."( Effects of clodronate-containing liposomes on testicular macrophages and Leydig cells in vitro.
Brigham, DE; Hutson, JC; Little, G; Lukyanenko, YO, 1997
)
0.3
"Solid state NMR is a method which can offer both molecular and crystal scale information, when either bulk or dosage forms of a drug can be altered by temperature or by loss of lattice waters or solvents."( A 31P CP/MAS NMR study on dehydration of disodium clodronate tetrahydrate.
Nikander, H; Pakkanen, TT; Pohjala, E; Timonen, JT, 1998
)
0.3
" These changes in 5HT corresponded well with each other in terms of both time course and dose-response relationship."( Displacement of platelets from blood to spleen following intravenous injection of liposomes encapsulating dichloromethylene bisphosphonate.
Endo, Y; Nakamura, M; Nitta, Y; Shibazaki, M, 1998
)
0.3
"), once a week for 3 or 6 months, the cumulative doses of both dosing regimens being 36, 84, and 300 mg/kg."( Effect of clodronate treatment on established bone loss in ovariectomized rats.
Hannuniemi, R; Isaksson, P; Kippo, K; Kuurtamo, P; Laurén, L; Osterman, T; Peng, Z; Sellman, R; Väänänen, HK; Virtamo, T, 1998
)
0.3
" The aim of the study was to derive data for the adjustment of dosage in haemodialysis patients."( Pharmacokinetics of clodronate in haemodialysis patients.
Ala-Houhala, I; Liukko-Sipi, S; Pasternack, A; Saha, H; Ylitalo, P, 1999
)
0.3
" The regimen of dosing intravenous clodronate in hypercalcaemia can also be used in haemodialysis patients."( Pharmacokinetics of clodronate in haemodialysis patients.
Ala-Houhala, I; Liukko-Sipi, S; Pasternack, A; Saha, H; Ylitalo, P, 1999
)
0.3
"Pharmacokinetics of orally given clodronate disodium, a drug for the treatment of hypercalcemia and bone resorption, were studied after a single dose of 400, 800 and 1600 mg given randomly to 11 healthy volunteers in a crossover manner, in 7-14 hospitalized cancer patients given 400, 800 and 1600 mg twice daily, each dosage for one week, and during the customary therapy in 15 additional cancer patients treated in hospital with 400 mg thrice daily for > or = 2 weeks."( Comparison of pharmacokinetics of clodronate after single and repeated doses.
Elo, HA; Holli, K; Juhakoski, A; Liukko-Sipi, S; Mönkkönen, J; Ylitalo, P; Ylitalo, R, 1999
)
0.3
" Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis."( Oral bisphosphonates: A review of clinical use in patients with bone metastases.
Berenson, J; Hortobagyi, G; Lipton, A; Major, PP, 2000
)
0.31
" Short-term bisphosphonate treatment at therapeutical dosage has been shown to be safe, but there are only a few studies concerning the long-term effects of bisphosphonates on the non-osteoporotic skeleton."( Effects of long-term administration of clodronate on growing rat bone.
Hannuniemi, R; Jalovaara, P; Jämsa, T; Kippo, K; Koivukangas, A; Tuukkanen, J, 2001
)
0.31
" Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients."( Bisphosphonates in the treatment of thalassemia-induced osteoporosis.
Crisafulli, A; Di Pietro, C; Frisina, N; Gaudio, A; Lasco, A; Meo, A; Morabito, N, 2002
)
0.31
" However, most relevant studies have been small, unblinded and short-term and have not systematically examined the effects of the dose and dosing intervals on bone mineral density and markers of bone turnover."( Clodronate: mechanisms of action on bone remodelling and clinical use in osteometabolic disorders.
Brandi, ML; Ghinoi, V, 2002
)
0.31
" The effect of intravenous infusions of bisphosphonates are, to a large extent, similar to equivalent intramuscular administrations, but doses and dosing intervals represent the critical issues."( Injectable bisphosphonates in the treatment of postmenopausal osteoporosis.
Adami, S; Crepaldi, G; Filipponi, P; Sartori, L, 2003
)
0.32
"Bisphosphonates exhibit direct antitumor activity in animal models, but only at high doses that are incompatible with the clinical dosing regimens approved for the treatment of cancer patients with skeletal metastases."( Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis.
Clézardin, P; Daubiné, F; Gasser, J; Green, J; Le Gall, C, 2007
)
0.34
" However, controversies remain over its optimal dosage and method of administration in the treatment of postmenopausal osteoporosis."( Clodronic acid in the treatment of postmenopausal osteoporosis.
Alagöl, F; Bayraktaroglu, T; Boztepe, H; Tanakol, R; Yarman, S, 2007
)
1.78
" This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover."( The use of bone markers in a 6-week study to assess the efficacy of oral clodronate in patients with metastatic bone disease.
Body, JJ; Brown, JE; Cameron, DA; Coleman, RE; Dewar, JA; Harnett, AN; McCloskey, EV; Purohit, OP; Ruutu, M; Tähtelä, R, 2007
)
0.34
"03) linear trend for a dose-response (0."( Intra-articular clodronate for the treatment of knee osteoarthritis: dose ranging study vs hyaluronic acid.
Adami, S; Bianchi, G; Lapadula, G; Olivieri, I; Ramonda, R; Rossini, M; Viapiana, O, 2009
)
0.35
" This new method can be utilized for routine analysis of FOS, CLO and ALN in dosage forms because of its efficiency, reliability, speed and simplicity."( Rapid analysis of alkylphosphonate drugs by capillary zone electrophoresis using indirect ultraviolet detection.
Prutthiwanasan, B; Suntornsuk, L, 2010
)
0.36
" The primary aim of this study was to evaluate the effects on lumbar and femoral bone mass density (BMD) after two different intramuscular (IM) dosing regimens of clodronate (CLD), a bisphosphonate shown to be efficacious in reducing the incidence of both vertebral and nonvertebral fractures."( "Twice-a-month" clodronate 200 mg IM: a new dosing regimen and improved therapy adherence in the treatment of postmenopausal osteoporosis.
Calcagnile, F; Muratore, M; Quarta, E; Quarta, L, 2010
)
0.36
"In agreement with published data, in our two groups of patients, therapy with IM CLD at the doses of 100 mg/week and 200 mg/2 weeks was shown to be effective in increasing BMD, without differences between the two dosing regimens in all assessed efficacy parameters."( "Twice-a-month" clodronate 200 mg IM: a new dosing regimen and improved therapy adherence in the treatment of postmenopausal osteoporosis.
Calcagnile, F; Muratore, M; Quarta, E; Quarta, L, 2010
)
0.36
" Other aspects of BP therapy that require further study include the optimization of dosing regimens for single agents and combinations in various clinical settings and the identification of prognostic factors that predict treatment outcomes."( Bisphosphonates as anticancer therapy for early breast cancer.
Jahanzeb, M; Mahtani, R, 2010
)
0.36
" Previous evidence suggests a direct dose-response relationship for the densitometric effect of clodronic acid."( Effects of two administration schemes of intramuscular clodronic acid on bone mineral density: a randomized, open-label, parallel-group study.
Frediani, B, 2011
)
0.83
" Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy."( Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.
Bertoldi, I; Cantarini, L; Filippou, G; Frediani, B; Galeazzi, M; Nicosia, A; Picerno, V; Pierguidi, S, 2013
)
0.39
" This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events."( Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.
Bertoldi, I; Cantarini, L; Filippou, G; Frediani, B; Galeazzi, M; Nicosia, A; Picerno, V; Pierguidi, S, 2013
)
0.39
" A number of treatment protocols with clodronate were used based on the common dosage regimen of 20 mg/kg in humans starting with the appearance of clinical signs on day 10 post-immunization."( Treatment for experimental autoimmune neuritis with clodronate (Bonefos).
Aronovich, R; Bina, H; Chapman, J; Katzav, A, 2013
)
0.39
" Semi-quantitative histopathology of the IM administration sites at day 1, 3, 7, 14, 21 and 28 after dosing with PP-LAI illustrated that CLO significantly decreased the rate and extent of the granulomatous inflammatory reaction."( The effect of macrophage and angiogenesis inhibition on the drug release and absorption from an intramuscular sustained-release paliperidone palmitate suspension.
Annaert, P; Darville, N; De Jonghe, S; De Meulder, M; Mariën, D; Rossenu, S; Sterkens, P; Van den Mooter, G; van Heerden, M; Vermeulen, A; Vynckier, A, 2016
)
0.43
" The aim of this study is to investigate the time- and dose-response effects of locally administered clodronate on tooth movement."( Dose- and time-dependent effects of clodronate on orthodontic tooth movement.
Džemidžić, V; Franić, M; Ivković, V; Lauc, T; Nakaš, E; Tiro, A; Zukanović, A, 2017
)
0.46
" Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required."( Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline.
Blanchette, PS; Clemons, MJ; Dhesy-Thind, S; Dillmon, MS; Fletcher, GG; Frank, ES; Gandhi, S; Gupta, R; Mates, M; Moy, B; Van Poznak, CH; Vandenberg, T, 2017
)
0.46
" This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies."( Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.
Al-Nawas, B; Jung, J; Kwon, YD; Pabst, AM; Park, JS; Righesso, L; Walter, C, 2018
)
0.48
" Further studies are warranted in horses undergoing exercise and those undergoing multiple dosing schemes."( Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.
Knych, HK; Krueger, CR; Leise, BS; Mitchell, CF, 2020
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
bone density conservation agentAn agent that inhibits bone resorption and/or favor bone mineralization and bone regeneration. Used to heal bone fractures and to treat bone diseases such as osteopenia and osteoporosis.
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
one-carbon compoundAn organic molecular entity containing a single carbon atom (C1).
1,1-bis(phosphonic acid)Any member of the class of phosphonic acids in which a carbon atom is directly attached to two phosphonic acid groups. They are analogues of pyrophosphates (with the central oxygen atom replaced by a carbon atom) and like pyrophosphates they tend to have a strong affinity for bone, so are frequently used for their antiresorptive and hypocalcaemic properties.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (12)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
thioredoxin reductaseRattus norvegicus (Norway rat)Potency0.63100.100020.879379.4328AID588453
GLS proteinHomo sapiens (human)Potency35.48130.35487.935539.8107AID624146
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency8.91250.035520.977089.1251AID504332
chromobox protein homolog 1Homo sapiens (human)Potency0.00470.006026.168889.1251AID488953
peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Homo sapiens (human)Potency26.85450.425612.059128.1838AID504536
M-phase phosphoprotein 8Homo sapiens (human)Potency21.19230.177824.735279.4328AID488949
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency60.11980.060110.745337.9330AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Type IV secretion-like conjugative transfer relaxase protein TraI Escherichia coli SMS-3-5Ki0.00300.00200.00270.0030AID328050
72 kDa type IV collagenaseHomo sapiens (human)IC50 (µMol)145.00000.00001.284810.0000AID291876
Stromelysin-1Homo sapiens (human)IC50 (µMol)300.00000.00001.148410.0000AID291878
Matrix metalloproteinase-9Homo sapiens (human)IC50 (µMol)320.00000.00000.705310.0000AID291877
Macrophage metalloelastaseHomo sapiens (human)IC50 (µMol)121.00000.00022.721710.0000AID291879
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (84)

Processvia Protein(s)Taxonomy
angiogenesis72 kDa type IV collagenaseHomo sapiens (human)
ovarian follicle development72 kDa type IV collagenaseHomo sapiens (human)
ovulation from ovarian follicle72 kDa type IV collagenaseHomo sapiens (human)
luteinization72 kDa type IV collagenaseHomo sapiens (human)
blood vessel maturation72 kDa type IV collagenaseHomo sapiens (human)
intramembranous ossification72 kDa type IV collagenaseHomo sapiens (human)
proteolysis72 kDa type IV collagenaseHomo sapiens (human)
negative regulation of cell adhesion72 kDa type IV collagenaseHomo sapiens (human)
heart development72 kDa type IV collagenaseHomo sapiens (human)
embryo implantation72 kDa type IV collagenaseHomo sapiens (human)
parturition72 kDa type IV collagenaseHomo sapiens (human)
response to xenobiotic stimulus72 kDa type IV collagenaseHomo sapiens (human)
response to mechanical stimulus72 kDa type IV collagenaseHomo sapiens (human)
peripheral nervous system axon regeneration72 kDa type IV collagenaseHomo sapiens (human)
response to activity72 kDa type IV collagenaseHomo sapiens (human)
protein metabolic process72 kDa type IV collagenaseHomo sapiens (human)
extracellular matrix disassembly72 kDa type IV collagenaseHomo sapiens (human)
protein catabolic process72 kDa type IV collagenaseHomo sapiens (human)
positive regulation of cell migration72 kDa type IV collagenaseHomo sapiens (human)
collagen catabolic process72 kDa type IV collagenaseHomo sapiens (human)
response to retinoic acid72 kDa type IV collagenaseHomo sapiens (human)
cellular response to reactive oxygen species72 kDa type IV collagenaseHomo sapiens (human)
response to nicotine72 kDa type IV collagenaseHomo sapiens (human)
endodermal cell differentiation72 kDa type IV collagenaseHomo sapiens (human)
response to hydrogen peroxide72 kDa type IV collagenaseHomo sapiens (human)
response to estrogen72 kDa type IV collagenaseHomo sapiens (human)
negative regulation of vasoconstriction72 kDa type IV collagenaseHomo sapiens (human)
ephrin receptor signaling pathway72 kDa type IV collagenaseHomo sapiens (human)
macrophage chemotaxis72 kDa type IV collagenaseHomo sapiens (human)
response to electrical stimulus72 kDa type IV collagenaseHomo sapiens (human)
response to hyperoxia72 kDa type IV collagenaseHomo sapiens (human)
face morphogenesis72 kDa type IV collagenaseHomo sapiens (human)
bone trabecula formation72 kDa type IV collagenaseHomo sapiens (human)
prostate gland epithelium morphogenesis72 kDa type IV collagenaseHomo sapiens (human)
cellular response to amino acid stimulus72 kDa type IV collagenaseHomo sapiens (human)
cellular response to interleukin-172 kDa type IV collagenaseHomo sapiens (human)
cellular response to estradiol stimulus72 kDa type IV collagenaseHomo sapiens (human)
cellular response to UV-A72 kDa type IV collagenaseHomo sapiens (human)
cellular response to fluid shear stress72 kDa type IV collagenaseHomo sapiens (human)
positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway72 kDa type IV collagenaseHomo sapiens (human)
response to amyloid-beta72 kDa type IV collagenaseHomo sapiens (human)
positive regulation of vascular associated smooth muscle cell proliferation72 kDa type IV collagenaseHomo sapiens (human)
extracellular matrix organization72 kDa type IV collagenaseHomo sapiens (human)
response to hypoxia72 kDa type IV collagenaseHomo sapiens (human)
tissue remodeling72 kDa type IV collagenaseHomo sapiens (human)
proteolysisStromelysin-1Homo sapiens (human)
extracellular matrix disassemblyStromelysin-1Homo sapiens (human)
protein catabolic processStromelysin-1Homo sapiens (human)
regulation of cell migrationStromelysin-1Homo sapiens (human)
collagen catabolic processStromelysin-1Homo sapiens (human)
positive regulation of protein-containing complex assemblyStromelysin-1Homo sapiens (human)
cellular response to reactive oxygen speciesStromelysin-1Homo sapiens (human)
innate immune responseStromelysin-1Homo sapiens (human)
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionStromelysin-1Homo sapiens (human)
cellular response to lipopolysaccharideStromelysin-1Homo sapiens (human)
cellular response to amino acid stimulusStromelysin-1Homo sapiens (human)
cellular response to UV-AStromelysin-1Homo sapiens (human)
cellular response to nitric oxideStromelysin-1Homo sapiens (human)
regulation of neuroinflammatory responseStromelysin-1Homo sapiens (human)
response to amyloid-betaStromelysin-1Homo sapiens (human)
negative regulation of reactive oxygen species metabolic processStromelysin-1Homo sapiens (human)
extracellular matrix organizationStromelysin-1Homo sapiens (human)
skeletal system developmentMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of protein phosphorylationMatrix metalloproteinase-9Homo sapiens (human)
proteolysisMatrix metalloproteinase-9Homo sapiens (human)
apoptotic processMatrix metalloproteinase-9Homo sapiens (human)
embryo implantationMatrix metalloproteinase-9Homo sapiens (human)
cell migrationMatrix metalloproteinase-9Homo sapiens (human)
extracellular matrix disassemblyMatrix metalloproteinase-9Homo sapiens (human)
macrophage differentiationMatrix metalloproteinase-9Homo sapiens (human)
collagen catabolic processMatrix metalloproteinase-9Homo sapiens (human)
cellular response to reactive oxygen speciesMatrix metalloproteinase-9Homo sapiens (human)
endodermal cell differentiationMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of apoptotic processMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of apoptotic processMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of DNA bindingMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of epidermal growth factor receptor signaling pathwayMatrix metalloproteinase-9Homo sapiens (human)
ephrin receptor signaling pathwayMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of keratinocyte migrationMatrix metalloproteinase-9Homo sapiens (human)
cellular response to lipopolysaccharideMatrix metalloproteinase-9Homo sapiens (human)
cellular response to cadmium ionMatrix metalloproteinase-9Homo sapiens (human)
cellular response to UV-AMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of release of cytochrome c from mitochondriaMatrix metalloproteinase-9Homo sapiens (human)
regulation of neuroinflammatory responseMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of receptor bindingMatrix metalloproteinase-9Homo sapiens (human)
response to amyloid-betaMatrix metalloproteinase-9Homo sapiens (human)
positive regulation of vascular associated smooth muscle cell proliferationMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of epithelial cell differentiation involved in kidney developmentMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of intrinsic apoptotic signaling pathwayMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of cation channel activityMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathwayMatrix metalloproteinase-9Homo sapiens (human)
extracellular matrix organizationMatrix metalloproteinase-9Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIMacrophage metalloelastaseHomo sapiens (human)
proteolysisMacrophage metalloelastaseHomo sapiens (human)
protein import into nucleusMacrophage metalloelastaseHomo sapiens (human)
extracellular matrix disassemblyMacrophage metalloelastaseHomo sapiens (human)
collagen catabolic processMacrophage metalloelastaseHomo sapiens (human)
positive regulation of interferon-alpha productionMacrophage metalloelastaseHomo sapiens (human)
wound healing, spreading of epidermal cellsMacrophage metalloelastaseHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIMacrophage metalloelastaseHomo sapiens (human)
lung alveolus developmentMacrophage metalloelastaseHomo sapiens (human)
regulation of defense response to virus by hostMacrophage metalloelastaseHomo sapiens (human)
positive regulation of epithelial cell proliferation involved in wound healingMacrophage metalloelastaseHomo sapiens (human)
elastin catabolic processMacrophage metalloelastaseHomo sapiens (human)
negative regulation of type I interferon-mediated signaling pathwayMacrophage metalloelastaseHomo sapiens (human)
positive regulation of type I interferon-mediated signaling pathwayMacrophage metalloelastaseHomo sapiens (human)
bronchiole developmentMacrophage metalloelastaseHomo sapiens (human)
cellular response to virusMacrophage metalloelastaseHomo sapiens (human)
response to amyloid-betaMacrophage metalloelastaseHomo sapiens (human)
negative regulation of endothelial cell-matrix adhesion via fibronectinMacrophage metalloelastaseHomo sapiens (human)
extracellular matrix organizationMacrophage metalloelastaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (13)

Processvia Protein(s)Taxonomy
fibronectin binding72 kDa type IV collagenaseHomo sapiens (human)
endopeptidase activity72 kDa type IV collagenaseHomo sapiens (human)
metalloendopeptidase activity72 kDa type IV collagenaseHomo sapiens (human)
serine-type endopeptidase activity72 kDa type IV collagenaseHomo sapiens (human)
protein binding72 kDa type IV collagenaseHomo sapiens (human)
metallopeptidase activity72 kDa type IV collagenaseHomo sapiens (human)
zinc ion binding72 kDa type IV collagenaseHomo sapiens (human)
endopeptidase activityStromelysin-1Homo sapiens (human)
metalloendopeptidase activityStromelysin-1Homo sapiens (human)
serine-type endopeptidase activityStromelysin-1Homo sapiens (human)
protein bindingStromelysin-1Homo sapiens (human)
peptidase activityStromelysin-1Homo sapiens (human)
metallopeptidase activityStromelysin-1Homo sapiens (human)
zinc ion bindingStromelysin-1Homo sapiens (human)
endopeptidase activityMatrix metalloproteinase-9Homo sapiens (human)
metalloendopeptidase activityMatrix metalloproteinase-9Homo sapiens (human)
serine-type endopeptidase activityMatrix metalloproteinase-9Homo sapiens (human)
protein bindingMatrix metalloproteinase-9Homo sapiens (human)
collagen bindingMatrix metalloproteinase-9Homo sapiens (human)
peptidase activityMatrix metalloproteinase-9Homo sapiens (human)
metallopeptidase activityMatrix metalloproteinase-9Homo sapiens (human)
zinc ion bindingMatrix metalloproteinase-9Homo sapiens (human)
identical protein bindingMatrix metalloproteinase-9Homo sapiens (human)
core promoter sequence-specific DNA bindingMacrophage metalloelastaseHomo sapiens (human)
endopeptidase activityMacrophage metalloelastaseHomo sapiens (human)
metalloendopeptidase activityMacrophage metalloelastaseHomo sapiens (human)
serine-type endopeptidase activityMacrophage metalloelastaseHomo sapiens (human)
calcium ion bindingMacrophage metalloelastaseHomo sapiens (human)
collagen bindingMacrophage metalloelastaseHomo sapiens (human)
zinc ion bindingMacrophage metalloelastaseHomo sapiens (human)
sequence-specific DNA bindingMacrophage metalloelastaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
collagen-containing extracellular matrix72 kDa type IV collagenaseHomo sapiens (human)
extracellular region72 kDa type IV collagenaseHomo sapiens (human)
extracellular space72 kDa type IV collagenaseHomo sapiens (human)
nucleus72 kDa type IV collagenaseHomo sapiens (human)
mitochondrion72 kDa type IV collagenaseHomo sapiens (human)
plasma membrane72 kDa type IV collagenaseHomo sapiens (human)
sarcomere72 kDa type IV collagenaseHomo sapiens (human)
collagen-containing extracellular matrix72 kDa type IV collagenaseHomo sapiens (human)
extracellular space72 kDa type IV collagenaseHomo sapiens (human)
extracellular regionStromelysin-1Homo sapiens (human)
nucleusStromelysin-1Homo sapiens (human)
mitochondrionStromelysin-1Homo sapiens (human)
cytosolStromelysin-1Homo sapiens (human)
extracellular matrixStromelysin-1Homo sapiens (human)
extracellular spaceStromelysin-1Homo sapiens (human)
extracellular regionMatrix metalloproteinase-9Homo sapiens (human)
extracellular spaceMatrix metalloproteinase-9Homo sapiens (human)
collagen-containing extracellular matrixMatrix metalloproteinase-9Homo sapiens (human)
extracellular exosomeMatrix metalloproteinase-9Homo sapiens (human)
tertiary granule lumenMatrix metalloproteinase-9Homo sapiens (human)
ficolin-1-rich granule lumenMatrix metalloproteinase-9Homo sapiens (human)
extracellular spaceMatrix metalloproteinase-9Homo sapiens (human)
extracellular regionMacrophage metalloelastaseHomo sapiens (human)
extracellular spaceMacrophage metalloelastaseHomo sapiens (human)
nucleusMacrophage metalloelastaseHomo sapiens (human)
cytoplasmMacrophage metalloelastaseHomo sapiens (human)
extracellular matrixMacrophage metalloelastaseHomo sapiens (human)
extracellular spaceMacrophage metalloelastaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (111)

Assay IDTitleYearJournalArticle
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1347151Optimization of GU AMC 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.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS 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.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID117180Decreased dry tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 100 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID117191Decreased wet tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 50 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID328050Inhibition of Escherichia coli F plasmid TraI relaxase Y16F mutant assessed as oriT ssDNA cleavage by competitive inhibition assay2007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID117190Decreased wet tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 25 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID328061Selectivity ratio, ratio of EC50 for Escherichia coli JS4 to ratio of EC50 for inhibition of conjugate DNA transfer between Escherichia coli JS10 and Escherichia coli JS42007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID654669Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in non-injected paw at 10 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID236912Permeability Coefficient in 2/4/A1 cell model2005Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2
Exploring the role of different drug transport routes in permeability screening.
AID224202Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 15 mg/kg in the injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID328053Inhibition of Escherichia coli F plasmid TraI relaxase Y16F mutant assessed as oriT ssDNA cleavage at 200 nM2007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID328060Selectivity ratio, ratio of EC50 for Escherichia coli JS10 to ratio of EC50 for inhibition of conjugate DNA transfer between Escherichia coli JS10 and Escherichia coli JS42007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID117186Decreased wet tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 100 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID123487Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 200 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID660277Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 72 hrs using 7.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID117189Decreased wet tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 200 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID654672Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma dry weight at 60 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID654677Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma wet weight at 25 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID654664Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in injected paw at 10 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID236914Permeability Coefficient in hexadecane membranes model2005Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2
Exploring the role of different drug transport routes in permeability screening.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID134333Compound was tested for anti-inflammatory activity in delayed type hypersensitivity granuloma upon 100 mg/kg peroral administration1998Bioorganic & medicinal chemistry letters, May-05, Volume: 8, Issue:9
Anti-inflammatory/antiarthritic ketonic bisphosphonic acid esters.
AID660271Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 3 hrs using 2.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID521220Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay2007Nature chemical biology, May, Volume: 3, Issue:5
Chemical genetics reveals a complex functional ground state of neural stem cells.
AID328054Inhibition of Escherichia coli F plasmid TraI relaxase Y16F mutant assessed as oriT ssDNA cleavage at 200 nM2007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID224203Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 15 mg/kg in the non-injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID660275Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 48 hrs using 5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID291878Inhibition of human recombinant MMP3 after 1 hr2007Journal of medicinal chemistry, Jul-26, Volume: 50, Issue:15
Platinum complexes can inhibit matrix metalloproteinase activity: platinum-diethyl[(methylsulfinyl)methyl]phosphonate complexes as inhibitors of matrix metalloproteinases 2, 3, 9, and 12.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID224204Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 30 mg/kg in the injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID224206Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 5 mg/kg in the injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID236268Fraction absorbed in human intestine after oral administration compound was measured2005Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2
Exploring the role of different drug transport routes in permeability screening.
AID123486Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 15 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID127978Compound was tested for antiarthritic activity in murine model of antigen-induced arthritis upon 100 mg/kg peroral administration1998Bioorganic & medicinal chemistry letters, May-05, Volume: 8, Issue:9
Anti-inflammatory/antiarthritic ketonic bisphosphonic acid esters.
AID123492Inhibition of delayed type hypersensitivity granuloma results at 100 mg/kg in dry weight1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID236916Percentage of mass balance in hexadecane membranes model2005Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2
Exploring the role of different drug transport routes in permeability screening.
AID328058Selectivity ratio, ratio of EC50 for Escherichia coli JS4 to EC50 for Escherichia coli JS102007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID224080Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 10 mg/kg in the injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID386623Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy2008Journal of medicinal chemistry, Oct-09, Volume: 51, Issue:19
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID291876Inhibition of human recombinant MMP2 after 1 hr2007Journal of medicinal chemistry, Jul-26, Volume: 50, Issue:15
Platinum complexes can inhibit matrix metalloproteinase activity: platinum-diethyl[(methylsulfinyl)methyl]phosphonate complexes as inhibitors of matrix metalloproteinases 2, 3, 9, and 12.
AID123484Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 10 mg/kg in the non-injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID328059Selectivity ratio, ratio of EC50 for inhibition of conjugate DNA transfer between Escherichia coli JS10 and Escherichia coli JS4 to EC50 for Escherichia coli JS102007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1894079Anti-osteoclast activity rat assessed as inhibition of bone resorption relative to control2021Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3
Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID117181Decreased dry tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 100 mg/kg after 9 days1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID291879Inhibition of human recombinant MMP12 after 1 hr2007Journal of medicinal chemistry, Jul-26, Volume: 50, Issue:15
Platinum complexes can inhibit matrix metalloproteinase activity: platinum-diethyl[(methylsulfinyl)methyl]phosphonate complexes as inhibitors of matrix metalloproteinases 2, 3, 9, and 12.
AID236913Permeability Coefficient in Caco-2 cell culture model2005Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2
Exploring the role of different drug transport routes in permeability screening.
AID117184Decreased dry tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 50 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID328055Inhibition of conjugate DNA transfer between tetracycline-resistant F plasmid positive Escherichia coli JS10 to streptomycin-resistant F plasmid deficient Escherichia coli JS42007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID291877Inhibition of human recombinant MMP9 after 1 hr2007Journal of medicinal chemistry, Jul-26, Volume: 50, Issue:15
Platinum complexes can inhibit matrix metalloproteinase activity: platinum-diethyl[(methylsulfinyl)methyl]phosphonate complexes as inhibitors of matrix metalloproteinases 2, 3, 9, and 12.
AID117183Decreased dry tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 25 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID328057Cytotoxicity against streptomycin-resistant F plasmid deficient Escherichia coli JS42007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID117187Decreased wet tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 100 mg/kg after 9 days1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID224205Inhibition of rat adjuvant induced polyarthritis (AIP) at the dose of 30 mg/kg in the non-injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID654666Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in non-injected paw at 50 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID134335Compound was tested for antiarthritic activity in murine model of antigen-induced arthritis upon 100 mg/kg peroral administration1998Bioorganic & medicinal chemistry letters, May-05, Volume: 8, Issue:9
Anti-inflammatory/antiarthritic ketonic bisphosphonic acid esters.
AID654676Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma wet weight at 60 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID123489Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 5 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID654662Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in injected paw at 30 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID1226177Half life in human plasma at 2.5 to 4 mg/kg, iv2015ACS medicinal chemistry letters, Apr-09, Volume: 6, Issue:4
Structural requirements for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID123485Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 100 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID660281Distribution coefficient, log D of the compound at pH 7.42012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID654668Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in non-injected paw at 20 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID654671Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma dry weight at 100 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID123493Inhibition of delayed type hypersensitivity granuloma results at 100 mg/kg in wet weight1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID117182Decreased dry tissue weight of DTH-GRA from mice was determined after (sc) administration of a dose of 200 mg/kg1994Journal of medicinal chemistry, Dec-23, Volume: 37, Issue:26
Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID1226174Binding affinity to hydroxyapatite at 3.2 to 3.7 mM after 1 hr by NMR analysis relative to control2015ACS medicinal chemistry letters, Apr-09, Volume: 6, Issue:4
Structural requirements for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters.
AID123491Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 50 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID660282Distribution coefficient, log D of the compound at pH 1.52012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID654675Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma wet weight at 100 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID654673Antiinflammatory activity in methylated bovine serum albumin sensitized delayed-type hypersensitivity granuloma mouse model assessed as reduction of granuloma dry weight at 25 mg/kg, sc qd for 9 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID660273Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 24 hrs using 2.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID127976Compound was tested for anti-inflammatory activity in delayed type hypersensitivity granuloma upon 100 mg/kg peroral administration1998Bioorganic & medicinal chemistry letters, May-05, Volume: 8, Issue:9
Anti-inflammatory/antiarthritic ketonic bisphosphonic acid esters.
AID660279Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 96 hrs using 10 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID654663Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in injected paw at 20 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID123490Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 5 mg/kg in the non-injected paw1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID654661Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in injected paw at 50 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID328056Cytotoxicity against tetracycline-resistant F plasmid positive Escherichia coli JS102007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID654667Antiarthritic activity in complete Freund's adjuvant-induced rat arthritis model assessed as reduction of paw volume in non-injected paw at 30 mg/kg, sc qd for 28 days2012European journal of medicinal chemistry, May, Volume: 51Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation.
AID123488Inhibition of antigen-induced polyarthritis (AIP) in mice at the dose of 30 mg/kg1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,662)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990200 (12.03)18.7374
1990's423 (25.45)18.2507
2000's500 (30.08)29.6817
2010's433 (26.05)24.3611
2020's106 (6.38)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 28.97

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 Index28.97 (24.57)
Research Supply Index7.58 (2.92)
Research Growth Index4.74 (4.65)
Search Engine Demand Index40.31 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (28.97)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials210 (12.01%)5.53%
Reviews0 (0.00%)6.00%
Reviews175 (10.01%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies80 (4.58%)4.05%
Observational0 (0.00%)0.25%
Observational1 (0.06%)0.25%
Other10 (100.00%)84.16%
Other1,282 (73.34%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (14)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
The Effect of Combined Drug Therapy in Lateral Fragility Fractures of the Femur:a Clinical Study [NCT05183308]50 participants (Actual)Observational2019-05-01Completed
A Clinical Trial Comparing Adjuvant Clodronate Therapy vs Placebo in Early-Stage Breast Cancer Patients Receiving Systemic Chemotherapy and/or Hormonal Therapy or No Therapy [NCT00009945]Phase 33,323 participants (Actual)Interventional2001-01-31Completed
Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer [NCT00127205]Phase 36,097 participants (Actual)Interventional2005-07-31Completed
MULTICENTRE, RANDOMIZED, OPEN-LABEL, TWO-ARM PARALLEL GROUPS, ACTIVE CONTROLLED STUDY DESIGN TO DEMONSTRATE EFFICACY AND TOLERABILITY OF CLODRONATE 200 MG/4 ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE EVERY OTHER WEEK VS CLODRONATE 100 MG/3,3ML SO [NCT01348243]Phase 3260 participants (Actual)Interventional2011-10-31Completed
Randomized Clinical Trial Evaluating Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy: the PENTOCLO Trial [NCT01291433]Phase 359 participants (Actual)Interventional2011-03-31Completed
BONA (Adherence of Patients to Bonefos Therapy). Prospective Observational Non-interventional Study of Adherence of Patients to Bonefos Medication in Relation to Analgesic Effect and Incidence of Skeletal Events [NCT01198457]147 participants (Actual)Observational2009-01-31Completed
Randomized Clinical Trial on the Effectts of Estradiol 2 mg + NETA 1 mg With or Without Clodronate on Bone Mineral Density and Bone Markers of Osteoporotic Postmenopausal 167 Finnish Women. [NCT00877097]167 participants (Actual)Interventional1996-07-31Completed
Combination Therapy: Hyperbaric Oxygen and PENTOCLO for Treatment of Osteoradionecrosis of the Mandible, a Pilot Randomized Control Trial [NCT06055257]Phase 324 participants (Anticipated)Interventional2023-12-15Not yet recruiting
Osteoradionecrosis and PENTOCLO Protocol: Retrospective Study. [NCT04097847]96 participants (Actual)Observational2017-06-02Completed
Long-Term Bone Quality in Women With Breast Cancer (A Companion Study to S0307) [NCT00873808]0 participants (Actual)Observational2008-10-31Withdrawn(stopped due to lack of accrual)
Bonefos and the Consumption of Analgesics. Influence of Clodronate on Analgesics Consumption Among Patients With Bone Metastasis [NCT00909142]149 participants (Actual)Observational2007-04-30Completed
Bisphosphonates and Impaction Grafting in Hip Revision Evaluated With Radiostereophotogrametri. A Randomized, Double-blind Study in Patients Operated for Aseptic Loosening and Osteolysis. [NCT00658268]Phase 232 participants (Actual)Interventional2008-03-31Completed
Could the Intra-operative Clodronate Rinsing Improve the Integration of the Femoral Stem in a Prospective, Double-blinded, Randomized, Placebo-controlled Clinical RSA-study [NCT03803839]Early Phase 119 participants (Actual)Interventional2004-03-26Completed
Randomized Placebo-Controlled Trial of Mitoxantrone/Prednisone and Clodronate Versus Mitoxantrone/Prednisone Alone in Patients With Hormone Refractory Metastatic Prostate Cancer and Pain [NCT00003232]Phase 3227 participants (Actual)Interventional1997-11-24Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00009945 (5) [back to overview]Disease Free Survival.
NCT00009945 (5) [back to overview]Incidence of Non-skeletal Metastasis
NCT00009945 (5) [back to overview]Overall Survival
NCT00009945 (5) [back to overview]Relapse Free Survival
NCT00009945 (5) [back to overview]Skeletal Metastasis Free Survival
NCT00127205 (4) [back to overview]Disease-free Survival
NCT00127205 (4) [back to overview]Overall Survival
NCT00127205 (4) [back to overview]Distributions of Sites of First Recurrence on the Three Arms.
NCT00127205 (4) [back to overview]Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Disease Free Survival.

Time to first event where an event is any recurrences, 2nd primary or death to determine the percentage of patients disease free at 8 years (NCT00009945)
Timeframe: 8 years

Interventionpercentage of patients (Number)
Arm 1: Clodronate81.0
Arm 2: Placebo79.6

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Incidence of Non-skeletal Metastasis

Time from randomization to incidence of non-skeletal metastasis to determine the percentage of patients free from non-skeletal metastasis at 8 years (NCT00009945)
Timeframe: 8 years

Interventionpercentage of patients (Number)
Arm 1: Clodronate94.8
Arm 2: Placebo93.2

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Overall Survival

Time from randomization to any death to determine the percentage of patients alive at 8 years (NCT00009945)
Timeframe: 8 years

Interventionpercentage of patients (Number)
Arm 1: Clodronate90.6
Arm 2: Placebo89.3

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Relapse Free Survival

Time from randomization to any local, regional, or distant recurrence of breast cancer to determine the percentage of patients relapse free at 8 years (NCT00009945)
Timeframe: 8 years

Interventionpercentage of patients (Number)
Arm 1: Clodronate89.9
Arm 2: Placebo88.3

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Skeletal Metastasis Free Survival

Time from randomization to first diagnosis of skeletal metastasis to determine the percentage of patient free of skeletal metastasis at 8 years (NCT00009945)
Timeframe: 8 years

Interventionpercentage of patients (Number)
Arm 1: Clodronate95.7
Arm 2: Placebo94.6

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Disease-free Survival

Time from date of registration to date of first observation of recurrence or death due to any cause. Patients last known to be alive who have not experienced recurrence of disease are censored at their last contact date. The outcome for the disease-free survival will be presented as 5 year survival rate. (NCT00127205)
Timeframe: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

Interventionpercentage of analyzed participants (Number)
Arm I Zoledronate88
Arm II Clodronate88
Arm III Ibandronate87

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Overall Survival

Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date. The outcome for overall survival will be presented as 5 year overall survival rate. (NCT00127205)
Timeframe: follow up completed every 6 months for 5 years and then annually for 5 years or until death

Interventionpercentage of analyzable patients (Number)
Arm I Zoledronate93
Arm II Clodronate92
Arm III Ibandronate93

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Distributions of Sites of First Recurrence on the Three Arms.

All sites of invasive disease documented within 30 days of first documentation of invasive recurrence. (NCT00127205)
Timeframe: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

,,
InterventionParticipants (Count of Participants)
Local/Regional onlyContralateral onlyDistant recurrenceUnknown location of recurrenceBone as 1st site of distant recurrenceBone onlyBone and nodes onlyBone and other distant sites (beside nodes)Liver/lung/other visceral without bone recurrenceBrain/other CNS (+/- any other site)
Arm I Zoledronate411721810110622465731
Arm II Clodronate551820715108482586724
Arm III Ibandronate36171461082442364022

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