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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:20 UTC
HMDB IDHMDB14858
Secondary Accession NumbersNone
Metabolite Identification
Common NameClodronate
DescriptionClodronate 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.
Structure
Thumb
Synonyms
ValueSource
(dichloro-phosphono-Methyl)-phosphonic acidChEBI
(Dichloromethylene)bisphosphonic acidChEBI
(Dichloromethylene)diphosphonic acidChEBI
Acide clodroniqueChEBI
acido ClodronicoChEBI
Acidum clodronicumChEBI
ClodronateChEBI
ClodronsaeureChEBI
Dichloromethylene-1,1-bisphosphonic acidChEBI
Dichloromethylene-1,1-diphosphonic acidChEBI
Dichloromethylidene diphosphonateChEBI
(dichloro-phosphono-Methyl)-phosphonateGenerator
(Dichloromethylene)bisphosphonateGenerator
(Dichloromethylene)diphosphonateGenerator
Dichloromethylene-1,1-bisphosphonateGenerator
Dichloromethylene-1,1-diphosphonateGenerator
Dichloromethylidene diphosphonic acidGenerator
Chemical FormulaCH4Cl2O6P2
Average Molecular Weight244.892
Monoisotopic Molecular Weight243.886016298
IUPAC Name[dichloro(phosphono)methyl]phosphonic acid
Traditional Nameclodronate
CAS Registry Number10596-23-3
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 KeyInChIKey=ACSIXWWBWUQEHA-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Organophosphonic acid
  • Halomethane
  • Hydrocarbon derivative
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antihypocalcemic Agents
  • Antineoplastic Agents
  • Bisphosphonates
  • Bone Density Conservation Agents
  • Osteoporosis Prophylactic
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point250 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility7.47e+00 g/LNot Available
LogP-2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.47 mg/mLALOGPS
logP0.16ALOGPS
logP-0.067ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)0.62ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.06 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity38.21 m3·mol-1ChemAxon
Polarizability15.3 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00720
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00720
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-4 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00720
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID23731
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkClodronate
NuGOwiki LinkHMDB14858
Metagene LinkHMDB14858
METLIN IDNot Available
PubChem Compound25419
PDB IDNot Available
ChEBI ID110423
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
References
  1. Liu L, Igarashi K, Kanzaki H, Chiba M, Shinoda H, Mitani H: Clodronate inhibits PGE(2) production in compressed periodontal ligament cells. J Dent Res. 2006 Aug;85(8):757-60. [16861295 ]
General function:
Involved in transporter activity
Specific function:
Catalyzes the exchange of ADP and ATP across the mitochondrial inner membrane
Gene Name:
SLC25A4
Uniprot ID:
P12235
Molecular weight:
33064.3
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [11961144 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in transporter activity
Specific function:
Catalyzes the exchange of ADP and ATP across the mitochondrial inner membrane
Gene Name:
SLC25A5
Uniprot ID:
P05141
Molecular weight:
32895.0
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [11961144 ]
General function:
Involved in transporter activity
Specific function:
Catalyzes the exchange of ADP and ATP across the mitochondrial inner membrane. May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis
Gene Name:
SLC25A6
Uniprot ID:
P12236
Molecular weight:
32866.0
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [11961144 ]