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

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

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
Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid myopathy.	1999	10638776
Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.	2001	11438040
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
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
The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer.	2001 Apr 20	11308252
Adjuvant bisphosphonate therapy: the future.	2001 Aug	11544582
Bisphosphonates in the prevention of bone metastases: current evidence.	2001 Aug	11544581
Disodium clodronate in the treatment of diffuse sclerosing osteomyelitis (DSO) of the mandible.	2001 Aug	11518354
Effects of long-term administration of clodronate on growing rat bone.	2001 Dec	11800232
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
The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer.	2001 Jan	11125382
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
Macrophage depletion prevents leukocyte adhesion and disease induction in experimental melanin-protein induced uveitis.	2001 Jul	11428867
Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma.	2001 Jun	11442499
The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro.	2001 Jun	11395574
A method for the selective depletion of perivascular and meningeal macrophages in the central nervous system.	2001 Jun 1	11438173
Atypical familial Paget's disease of bone.	2001 May	11394627
Bisphosphonates in the treatment of metastatic breast cancer.	2001 Oct	12013536
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
Recent advances in breast cancer (the Twenty-fourth San Antonio Breast Cancer Symposium, December, 2001).	2002	11999142
The present and future role of bisphosphonates in the management of patients with breast cancer.	2002	11879556
Bisphosphonates for breast cancer.	2002	11869664
Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.	2002 Feb	11870415
Reduction of instability-induced bone resorption using bisphosphonates: high doses are needed in rats.	2002 Jan	11928907
Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice.	2002 Jun	12054176
Bisphosphonate prodrugs.	2002 Jun	12052172
Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice.	2002 Jun	12003780
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 Mar	11984068
Disodium chlodronate prevents bone resorption in experimental periodontitis in rats.	2002 Mar	11924589
[Bisphosphonate therapy in Paget disease?].	2002 Mar 22	11907869
Complete healing of severe osteoradionecrosis with treatment combining pentoxifylline, tocopherol and clodronate.	2002 May	12036843
Effects of topical administration of clodronate on alveolar bone resorption in rats with experimental periodontitis.	2002 May	12027248
Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease.	2002 May 20	12031126
The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells.	2002 May 6	11986784

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

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

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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