ContaminantDB: Clodronate

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (9)XML

Record Information

Version

1.0

Creation Date

2009-07-15 20:41:25 UTC

Update Date

2026-03-26 22:46:37 UTC

Accession Number

CHEM002109

Identification

Common Name

Clodronate

Class

Small Molecule

Description

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.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins

Contaminant Type

Antihypocalcemic Agent
Antineoplastic Agent
Bisphosphonate
Bone Density Conservation Agent
Drug
Metabolite
Organic Compound
Organochloride
Osteoporosis Prophylactic
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(Dichloro-phosphono-methyl)-phosphonic acid	ChEBI
(Dichloromethylene)bisphosphonic acid	ChEBI
(Dichloromethylene)diphosphonic acid	ChEBI
Acide clodronique	ChEBI
Acido clodronico	ChEBI
Acidum clodronicum	ChEBI
Clodronsaeure	ChEBI
Dichloromethylene-1,1-bisphosphonic acid	ChEBI
Dichloromethylene-1,1-diphosphonic acid	ChEBI
Dichloromethylidene diphosphonate	ChEBI
(Dichloro-phosphono-methyl)-phosphonate	Generator
(Dichloromethylene)bisphosphonate	Generator
(Dichloromethylene)diphosphonate	Generator
Dichloromethylene-1,1-bisphosphonate	Generator
Dichloromethylene-1,1-diphosphonate	Generator
Dichloromethylidene diphosphonic acid	Generator
Clodronic acid	Generator
Acid, dichloromethanediphosphonic	HMDB
Bonefos	HMDB
Clodronate disodium	HMDB
Dichloromethanediphosphonate	HMDB
Dichloromethylene diphosphonate	HMDB
Acid, clodronic	HMDB
Dichloromethane diphosphonate	HMDB
Dichloromethylene biphosphonate	HMDB
Diphosphonate, dichloromethane	HMDB
Biphosphonate, dichloromethylene	HMDB
Diphosphonate, dichloromethylene	HMDB
Disodium, clodronate	HMDB
Sodium, clodronate	HMDB
CL2MDP	HMDB
Clodronate sodium	HMDB
Dichloromethanediphosphonic acid	HMDB
Dichloromethylenebisphosphonate	HMDB
Clodronate	ChEBI

Chemical Formula

CH₄Cl₂O₆P₂

Average Molecular Mass

244.892 g/mol

Monoisotopic Mass

243.886 g/mol

CAS Registry Number

10596-23-3

IUPAC Name

[dichloro(phosphono)methyl]phosphonic acid

Traditional Name

clodronate

SMILES

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

InChI Identifier

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

InChI Key

ACSIXWWBWUQEHA-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Organic phosphonic acids and derivatives

Sub Class

Bisphosphonates

Direct Parent

Bisphosphonates

Alternative Parents

Substituents

Bisphosphonate
Organophosphonic acid
Organic oxygen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Organophosphorus compound
Organochloride
Organohalogen compound
Alkyl halide
Alkyl chloride
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

one-carbon compound (CHEBI:110423 )
organochlorine compound (CHEBI:110423 )
1,1-bis(phosphonic acid) (CHEBI:110423 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	250°C
Boiling Point	Not Available
Solubility	395 mg/L

Predicted Properties

Property	Value	Source
Water Solubility	7.47 g/L	ALOGPS
logP	0.16	ALOGPS
logP	-0.067	ChemAxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	0.62	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	115.06 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	38.21 m³·mol⁻¹	ChemAxon
Polarizability	15.3 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9040000000-af3c2e18902e147f8d42	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-1190000000-c4ab9891e7e58566d92f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03ed-3940000000-c29d8ff76855c0aaef6c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9000000000-01a0eea1cf84ed37407a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03dl-0950000000-1845236a124e15b5c59b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-006x-1390000000-3ae475737e6b4b8c7664	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-9000000000-974168c5223d898e9a79	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000x-6090000000-8989f8d7643382de70bc	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-2900000000-95542c15d3d7df8beff2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03ea-4900000000-e088c1d2fe760f01f20d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00dl-0090000000-125baa903034088b47b6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00fr-6590000000-8d753c1dbb524b991ddf	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00di-1090000000-29462d306ece6e9df24d	Spectrum

Toxicity Profile

Route of Exposure

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

Mechanism of Toxicity

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.

Metabolism

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.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

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

Symptoms

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

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB00720

HMDB ID

HMDB0014858

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

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

MSDS

Link

General References

1. https://www.ncbi.nlm.nih.gov/pubmed/?term=15658873

2. https://www.ncbi.nlm.nih.gov/pubmed/?term=7818726

3. https://www.ncbi.nlm.nih.gov/pubmed/?term=8421279

Clodronate (CHEM002109)

Structure for CHEM002109: Clodronate