CLODRONIC ACID

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 Search

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

Description
Sources: https://www.medicines.org.uk/emc/medicine/311 |

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ADP/ATP translocase 2 3 Target ID: P05141 Gene ID: 292.0 Gene Symbol: SLC25A5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11961144	Inhibitor 8297
ADP/ATP translocase 3 3 Target ID: P12236 Gene ID: 293.0 Gene Symbol: SLC25A6 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11961144	Inhibitor 8297
ADP/ATP translocase 1 3 Target ID: P12235 Gene ID: 291.0 Gene Symbol: SLC25A4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11961144	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.medicines.org.uk/emc/medicine/311	Primary		Approved 8429	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.
Multiple myeloma 159 Sources: https://www.medicines.org.uk/emc/medicine/311	Primary		Approved 8429	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

Title	Date	PubMed
Bisphosphonates in multiple myeloma.	2001	11687178
Reduction of visible bone metastases by clodronate therapy in breast cancer.	2001	11501775
Effect of intramuscular clodronate on bone mass and metabolism in osteoporotic women.	2001	11392061
One-month follow-up of patients treated by intravenous clodronate for acute pain induced by osteoporotic vertebral fracture.	2001	11392057
Bone mineral density in multiple myeloma patients after intravenous clodronate therapy.	2001	11382140
Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP).	2001 Apr	11380601
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	11354395
Alveolar macrophages, surfactant lipids, and surfactant protein B regulate the induction of immune responses via the airways.	2001 Apr	11306439
Analgesic effect of bisphosphonates in mice.	2001 Apr	11275384
Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice.	2001 Apr 1	11254718
Expression of Th2 cytokines decreases the development of and improves Behçet's disease-like symptoms induced by herpes simplex virus in mice.	2001 Apr 15	11262199
The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer.	2001 Apr 20	11308252
[Bisphosphonates in the treatment of breast carcinoma].	2001 Aug	11926150
[Use of clodronic acid in mineral metabolism conditions: state of the art in 2000].	2001 Aug	11535969
Novel therapeutic approaches to cancer patients with bone metastasis.	2001 Dec	11738947
Treatment of osteoporosis with bisphosphonates.	2001 Feb	11285996
A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: a dynamic histomorphometric and gene expression study.	2001 Feb	11172684
Effects of calcium and lipophilicity on transport of clodronate and its esters through Caco-2 cells.	2001 Feb 1	11165101
Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-gamma-dependent mechanism.	2001 Feb 1	11160186
Depletion of systemic macrophages by liposome-encapsulated clodronate attenuates striatal macrophage invasion and neurodegeneration following local endotoxin infusion in gerbils.	2001 Feb 16	11172745
Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial.	2001 Jan 1	11134190
[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases].	2001 Jul	11495824
The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro.	2001 Jun	11395574
Kupffer cells and neutrophils as paracrine regulators of the heme oxygenase-1 gene in hepatocytes after hemorrhagic shock.	2001 Jun	11386615
Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection.	2001 Jun	11356791
Use of bisphosphonates for the treatment of metastatic bone pain. A survey of palliative physicians in the UK.	2001 Mar	11301665
Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: sensitization and cross-sensitization effects.	2001 Mar	11285013
Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis.	2001 Mar	11248662
Incidence and severity of herpetic stromal keratitis: impaired by the depletion of lymph node macrophages.	2001 Mar	11180975
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	11292289
Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro.	2001 May	11344045
Induction of proliferation and augmented cytotoxicity of gammadelta T lymphocytes by bisphosphonate clodronate.	2001 May 1	11345090
Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats.	2001 Nov	11737856
Bisphosphonates in the treatment of metastatic breast cancer.	2001 Oct	12013536
Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease.	2001 Oct	11762816
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	11595616
Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis.	2001 Oct 1	11564810
Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis.	2001 Oct 15	11591794
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	11592386
Treatment of complex regional pain syndrome type I.	2002	11900471
The present and future role of bisphosphonates in the management of patients with breast cancer.	2002	11879556
Electrospray ionization mass spectrometry and tandem mass spectrometry of clodronate and related bisphosphonate and phosphonate compounds.	2002 Feb	11857764
The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis.	2002 Jan	11777538
Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?	2002 Jan-Feb	11791086
Bisphosphonate prodrugs.	2002 Jun	12052172
Disodium chlodronate prevents bone resorption in experimental periodontitis in rats.	2002 Mar	11924589
Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite.	2002 May	11961144

Patents

Sample Use Guides

In Vivo Use Guide

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

Unknown

Name

Type

Language

CLODRONIC ACID

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