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 8504
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 8504
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 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 432 Sources: https://www.medicines.org.uk/emc/medicine/311	Primary		Approved 8583	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 8583	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
The difluoromethylenesulfonic acid group as a monoanionic phosphate surrogate for obtaining PTP1B inhibitors.	2002-07	11983529
Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice.	2002-06	12054176
Bisphosphonate prodrugs.	2002-06	12052172
Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice.	2002-06	12003780
Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease.	2002-05-20	12031126
The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells.	2002-05-06	11986784
Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway.	2002-05-01	11980672
Complete healing of severe osteoradionecrosis with treatment combining pentoxifylline, tocopherol and clodronate.	2002-05	12036843
Effects of topical administration of clodronate on alveolar bone resorption in rats with experimental periodontitis.	2002-05	12027248
Macrophages are necessary for maximal nuclear factor-kappa B activation in response to endotoxin.	2002-05	11970909
Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite.	2002-05	11961144
Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia?	2002-04-22	11953878
[Bisphosphonate therapy in Paget disease?].	2002-03-22	11907869
Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines.	2002-03	11984068
Disodium chlodronate prevents bone resorption in experimental periodontitis in rats.	2002-03	11924589
Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate.	2002-03	11874245
Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status.	2002-02-01	11821470
Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.	2002-02	11870415
Clodronate in myelofibrosis: a case report.	2002-02	11863080
Electrospray ionization mass spectrometry and tandem mass spectrometry of clodronate and related bisphosphonate and phosphonate compounds.	2002-02	11857764
Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia.	2002-02	11841439
Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?	2002-01-16	11791086
Reduction of instability-induced bone resorption using bisphosphonates: high doses are needed in rats.	2002-01	11928907
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.	2002-01	11792566
The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis.	2002-01	11777538
Recent advances in breast cancer (the Twenty-fourth San Antonio Breast Cancer Symposium, December, 2001).	2002	11999142
Treatment of complex regional pain syndrome type I.	2002	11900471
Actions of bisphosphonates in animal models of breast cancer.	2002	11879558
Development of bisphosphonates.	2002	11879557
The present and future role of bisphosphonates in the management of patients with breast cancer.	2002	11879556
Direct effects of bisphosphonates on breast cancer cells.	2002	11879555
Bisphosphonates for breast cancer.	2002	11869664
Clinical and biochemical response to single infusion of clodronate in active rheumatoid arthritis--a double blind placebo controlled study.	2001-12	11822785
Effects of long-term administration of clodronate on growing rat bone.	2001-12	11800232
[Parenteral disodium-clodronate in patients with rheumatoid arthritis. A two-month open clinical study].	2001-12	11740429
Novel therapeutic approaches to cancer patients with bone metastasis.	2001-12	11738947
Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis.	2001-12	11728926
Long-term impact of chemotherapy-induced ovarian failure on bone mineral density (BMD) in premenopausal breast cancer patients. The effect of adjuvant clodronate treatment.	2001-12	11720830
The cellular uptake and metabolism of clodronate in RAW 264 macrophages.	2001-11	11758762
Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats.	2001-11	11737856
Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis.	2001-10-15	11591794
Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis.	2001-10-01	11564810
Bisphosphonates in the treatment of metastatic breast cancer.	2001-10	12013536
Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease.	2001-10	11762816
Paget's disease of the spine and its management.	2001-10	11718191
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.	2001-10	11595616
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.	2001-09	11592386
[Bisphosphonates in the treatment of breast carcinoma].	2001-08	11926150
Strategies for management of prostate cancer-related bone pain.	2001	11888345
Bisphosphonates in multiple myeloma.	2001	11687178

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

CLODRONATE

Preferred 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

Clodronic acid [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QM05BA02