U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula CH4Cl2O6P2
Molecular Weight 244.892
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLODRONIC ACID

SMILES

OP(O)(=O)C(Cl)(Cl)P(O)(O)=O

InChI

InChIKey=ACSIXWWBWUQEHA-UHFFFAOYSA-N
InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)

HIDE SMILES / InChI

Molecular Formula CH4Cl2O6P2
Molecular Weight 244.892
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Clodronate (also known as clodronic acid) is a drug used to treat a high level of calcium in the blood caused by changes in the body that happen with cancer. Clodronate is approved in some countries and is sold under trade trade name bonefos for oral use. Bonefos is indicated in the management of osteolytic lesions, hypercalcemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma. Bonefos is also indicated for the maintenance of clinically acceptable serum calcium levels in patients with hypercalcemia of malignancy initially treated with an intravenous bisphosphonate. Bonefos forms complexes with divalent metal ions, and therefore simultaneous administration with food, antacids and mineral supplements may impair absorption. It was suggested, that the mechanism of action of clodronate was involved osteoclast apoptosis.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P05141
Gene ID: 292.0
Gene Symbol: SLC25A5
Target Organism: Homo sapiens (Human)
Target ID: P12236
Gene ID: 293.0
Gene Symbol: SLC25A6
Target Organism: Homo sapiens (Human)
Target ID: P12235
Gene ID: 291.0
Gene Symbol: SLC25A4
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Bonefos

Approved Use

Bonefos tablets are indicated in the management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma. Bonefos tablets are also indicated for the maintenance of clinically acceptable serum calcium levels in patients with hypercalcaemia of malignancy initially treated with an intravenous bisphosphonate.
Primary
Bonefos

Approved Use

Bonefos tablets are indicated in the management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma. Bonefos tablets are also indicated for the maintenance of clinically acceptable serum calcium levels in patients with hypercalcaemia of malignancy initially treated with an intravenous bisphosphonate.
PubMed

PubMed

TitleDatePubMed
Bisphosphonates in multiple myeloma.
2001
Effect of intramuscular clodronate on bone mass and metabolism in osteoporotic women.
2001
Alterations in osteoclast morphology following long-term 17beta-estradiol administration in the mouse.
2001
Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP).
2001 Apr
Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000.
2001 Apr
Analgesic effect of bisphosphonates in mice.
2001 Apr
The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer.
2001 Apr 20
Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line.
2001 Apr 6
[Bisphosphonates in the treatment of breast carcinoma].
2001 Aug
Bisphosphonates in the prevention of bone metastases: current evidence.
2001 Aug
A combination of a chemically modified doxycycline and a bisphosphonate synergistically inhibits endotoxin-induced periodontal breakdown in rats.
2001 Aug
Clinical and biochemical response to single infusion of clodronate in active rheumatoid arthritis--a double blind placebo controlled study.
2001 Dec
Effects of long-term administration of clodronate on growing rat bone.
2001 Dec
Treatment of osteoporosis with bisphosphonates.
2001 Feb
[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases].
2001 Jul
Macrophage depletion prevents leukocyte adhesion and disease induction in experimental melanin-protein induced uveitis.
2001 Jul
Bisphosphonates may be useful in treatment of bone metastases.
2001 Jul 18
Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma.
2001 Jun
The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro.
2001 Jun
Kupffer cells and neutrophils as paracrine regulators of the heme oxygenase-1 gene in hepatocytes after hemorrhagic shock.
2001 Jun
Use of bisphosphonates for the treatment of metastatic bone pain. A survey of palliative physicians in the UK.
2001 Mar
Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: sensitization and cross-sensitization effects.
2001 Mar
An immunomodulatory procedure that stabilizes transgene expression and permits readministration of E1-deleted adenovirus vectors.
2001 Mar
Bone marrow transplant conditioning intensified with liposomal clodronate to eliminate residual host antigen presenting cells fails to ameliorate GVHD and increases PERI-BMT mortality.
2001 Mar 15
CD8+ phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis.
2001 May
Atypical familial Paget's disease of bone.
2001 May
Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro.
2001 May
The cellular uptake and metabolism of clodronate in RAW 264 macrophages.
2001 Nov
Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease.
2001 Oct
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.
2001 Oct
Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis.
2001 Oct 1
Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis.
2001 Oct 15
The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis.
2001 Sep
Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination.
2001 Sep
Actions of bisphosphonates in animal models of breast cancer.
2002
Development of bisphosphonates.
2002
The present and future role of bisphosphonates in the management of patients with breast cancer.
2002
Bisphosphonates for breast cancer.
2002
Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia?
2002 Apr 22
Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia.
2002 Feb
Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates on osteoclast precursors.
2002 Jan
Bisphosphonate prodrugs.
2002 Jun
Disodium chlodronate prevents bone resorption in experimental periodontitis in rats.
2002 Mar
[Bisphosphonate therapy in Paget disease?].
2002 Mar 22
Complete healing of severe osteoradionecrosis with treatment combining pentoxifylline, tocopherol and clodronate.
2002 May
Effects of topical administration of clodronate on alveolar bone resorption in rats with experimental periodontitis.
2002 May
Macrophages are necessary for maximal nuclear factor-kappa B activation in response to endotoxin.
2002 May
Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway.
2002 May 1
Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease.
2002 May 20
The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells.
2002 May 6
Patents

Patents

Sample Use Guides

A daily dose of 1600 mg should be taken as a single dose. When higher daily doses are used, the part of the dose exceeding 1600 mg should be taken separately (as a second dose) as recommended below.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: It was found that due to high bisphosphonate-bone binding affinity, bone surface exposure to clodronate for 3 min. had maximal resorption inhibition. The mechanism of action of both clodronate and zoledronic acid involved osteoclast apoptosis, whereas pamidronate had only minor apoptotic effect at dosages, which readily inhibited resorption. Zoledronic acid was not metabolised into an intracellular ATP-analogue in vitro in contrast to clodronate
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:25:45 GMT 2023
Edited
by admin
on Fri Dec 15 16:25:45 GMT 2023
Record UNII
0813BZ6866
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLODRONIC ACID
INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
CLODRONIC ACID [USAN]
Common Name English
PHOSPHONIC ACID, (DICHLOROMETHYLENE)BIS-
Common Name English
clodronic acid [INN]
Common Name English
CLODRONIC ACID [MI]
Common Name English
(Dichloromethylene)diphosphonic acid
Systematic Name English
CLODRONIC ACID [GREEN BOOK]
Common Name English
CLODRONIC ACID [MART.]
Common Name English
CLODRONATE
Common Name English
Clodronic acid [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-VATC QM05BA02
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
NCI_THESAURUS C443
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
NCI_THESAURUS C67439
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
WHO-ATC M05BA02
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
Code System Code Type Description
CAS
10596-23-3
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
NCI_THESAURUS
C61685
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
DRUG CENTRAL
690
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
PUBCHEM
25419
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
MERCK INDEX
m3635
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY Merck Index
ECHA (EC/EINECS)
234-212-1
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
WIKIPEDIA
CLODRONIC ACID
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
FDA UNII
0813BZ6866
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
INN
4147
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
DRUG BANK
DB00720
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
ChEMBL
CHEMBL12318
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
CHEBI
59585
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
DAILYMED
0813BZ6866
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
CHEBI
110423
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
SMS_ID
100000092584
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
MESH
D004002
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
RXCUI
3350
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID8046959
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
EVMPD
SUB06693MIG
Created by admin on Fri Dec 15 16:25:45 GMT 2023 , Edited by admin on Fri Dec 15 16:25:45 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
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ACTIVE MOIETY