T3D2663

2705 T3D2663

Clodronate

Clodronate is only found in individuals that have used or taken this drug. It is a diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [PubChem]The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Clodronate, like all biphosphonates, also binds protein-tyrosine-phosphatase. 10596-23-3

25419

CH4Cl2O6P2

243.886020 White powder.

250°C

395 mg/L

Oral, Intravenous. After oral administration, absorption is estimated at 1–3% of the ingested dose because of the low uptake from the gastrointestinal tract.

The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Clodronate, like all biphosphonates, also binds protein-tyrosine-phosphatase.

Clodronate is not metabolized in humans. It can be metabolized intracellularly to a beta-gamma-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Half Life: Approximately 13 hours. No indication of carcinogenicity to humans (not listed by IARC).

A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.

Decreases in serum calcium following substantial overdosage may be expected in some patients.

Signs and symptoms of hypocalcemia also may occur in some of these patients.

2009-07-15T20:41:25Z

2014-12-24T20:25:48Z

Clodronate

110423

Clodronic acid

DB00720

true

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

CH4Cl2O6P2

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

InChIKey=ACSIXWWBWUQEHA-UHFFFAOYSA-N

244.892

243.886016298

Exogenous Solid -2.4

HMDB14858

CHEMBL12318

23731

Fritz Demmer, Berthold Stemmle, “Clodronate-containing medicaments and a process for the preparation thereof.” U.S. Patent US4859472, issued September, 1980.