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Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:50 UTC

Update Date

2022-03-07 02:51:46 UTC

HMDB ID

HMDB0014858

Secondary Accession Numbers

HMDB14858

Metabolite Identification

Common Name

Clodronate

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.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

View in JSmol View Stereo Labels

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 Weight

244.892

Monoisotopic Molecular Weight

243.886016298

IUPAC Name

[dichloro(phosphono)methyl]phosphonic acid

Traditional Name

clodronate

CAS Registry Number

10596-23-3

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 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 )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Source

Exogenous

Exogenous (HMDB: HMDB0014858)

Process

Not Available

Role

Industrial application

Bone density conservation agent (HMDB: HMDB0014858)
Antineoplastic agent (HMDB: HMDB0014858)

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	250 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	7.47 g/L	Not Available
LogP	-2.4	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular 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	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DeepCCS	[M+H]+	119.402	30932474
DeepCCS	[M-H]-	115.819	30932474
DeepCCS	[M-2H]-	153.597	30932474
DeepCCS	[M+Na]+	129.109	30932474
AllCCS	[M+H]+	145.3	32859911
AllCCS	[M+H-H2O]+	142.0	32859911
AllCCS	[M+NH4]+	148.3	32859911
AllCCS	[M+Na]+	149.1	32859911
AllCCS	[M-H]-	134.6	32859911
AllCCS	[M+Na-2H]-	136.7	32859911
AllCCS	[M+HCOO]-	139.0	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Clodronate	OP(O)(=O)C(Cl)(Cl)P(O)(O)=O	3121.5	Standard polar	33892256
Clodronate	OP(O)(=O)C(Cl)(Cl)P(O)(O)=O	1668.9	Standard non polar	33892256
Clodronate	OP(O)(=O)C(Cl)(Cl)P(O)(O)=O	1848.7	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Clodronate,1TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	1918.3	Semi standard non polar	33892256
Clodronate,1TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	1647.9	Standard non polar	33892256
Clodronate,1TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	2402.0	Standard polar	33892256
Clodronate,2TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O)O	1937.6	Semi standard non polar	33892256
Clodronate,2TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O)O	1790.2	Standard non polar	33892256
Clodronate,2TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O)O	2066.7	Standard polar	33892256
Clodronate,2TMS,isomer #2	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C	1945.5	Semi standard non polar	33892256
Clodronate,2TMS,isomer #2	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C	1768.9	Standard non polar	33892256
Clodronate,2TMS,isomer #2	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C	2090.1	Standard polar	33892256
Clodronate,3TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1943.2	Semi standard non polar	33892256
Clodronate,3TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1850.1	Standard non polar	33892256
Clodronate,3TMS,isomer #1	C[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1961.0	Standard polar	33892256
Clodronate,4TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1943.9	Semi standard non polar	33892256
Clodronate,4TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1939.7	Standard non polar	33892256
Clodronate,4TMS,isomer #1	C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C)O[Si](C)(C)C	1871.2	Standard polar	33892256
Clodronate,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	2193.2	Semi standard non polar	33892256
Clodronate,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	1872.6	Standard non polar	33892256
Clodronate,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O	2539.1	Standard polar	33892256
Clodronate,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O)O	2412.3	Semi standard non polar	33892256
Clodronate,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O)O	2174.6	Standard non polar	33892256
Clodronate,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O)O	2344.6	Standard polar	33892256
Clodronate,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C(C)(C)C	2418.6	Semi standard non polar	33892256
Clodronate,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C(C)(C)C	2160.2	Standard non polar	33892256
Clodronate,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O)O[Si](C)(C)C(C)(C)C	2380.8	Standard polar	33892256
Clodronate,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2576.3	Semi standard non polar	33892256
Clodronate,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2368.8	Standard non polar	33892256
Clodronate,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2337.3	Standard polar	33892256
Clodronate,4TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2726.4	Semi standard non polar	33892256
Clodronate,4TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2562.9	Standard non polar	33892256
Clodronate,4TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OP(=O)(O[Si](C)(C)C(C)(C)C)C(Cl)(Cl)P(=O)(O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C	2326.1	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Clodronate GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9040000000-af3c2e18902e147f8d42	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Clodronate GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 10V, Positive-QTOF	splash10-0006-1190000000-c4ab9891e7e58566d92f	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 20V, Positive-QTOF	splash10-03ed-3940000000-c29d8ff76855c0aaef6c	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 40V, Positive-QTOF	splash10-001i-9000000000-01a0eea1cf84ed37407a	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 10V, Negative-QTOF	splash10-03dl-0950000000-1845236a124e15b5c59b	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 20V, Negative-QTOF	splash10-006x-1390000000-3ae475737e6b4b8c7664	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 40V, Negative-QTOF	splash10-004i-9000000000-974168c5223d898e9a79	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 10V, Positive-QTOF	splash10-000x-6090000000-8989f8d7643382de70bc	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 20V, Positive-QTOF	splash10-03di-2900000000-95542c15d3d7df8beff2	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 40V, Positive-QTOF	splash10-03ea-4900000000-e088c1d2fe760f01f20d	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 10V, Negative-QTOF	splash10-00dl-0090000000-125baa903034088b47b6	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 20V, Negative-QTOF	splash10-00fr-6590000000-8d753c1dbb524b991ddf	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Clodronate 40V, Negative-QTOF	splash10-00di-1090000000-29462d306ece6e9df24d	2021-10-11	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/PathBank	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB00720	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB00720	21059682	details

Abnormal Concentrations

Not Available

Predicted Concentrations

Biospecimen	Value	Original age	Original sex	Original condition	Comments
Blood	0.000 uM	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities
Blood	0.000 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB00720

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

23731

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Clodronic acid

METLIN ID

Not Available

PubChem Compound

25419

PDB ID

Not Available

ChEBI ID

110423

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Not Available

Enzymes

Enzyme Details

1. Prostaglandin G/H synthase 2

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

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. [PubMed:16861295 ]

Enzyme Details

2. ADP/ATP translocase 1

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

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. [PubMed:11961144 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzyme Details

3. ADP/ATP translocase 2

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

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. [PubMed:11961144 ]

Enzyme Details

4. ADP/ATP translocase 3

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

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. [PubMed:11961144 ]

Showing metabocard for Clodronate (HMDB0014858)

MOL for HMDB0014858 (Clodronate)

3D MOL for HMDB0014858 (Clodronate)

3D SDF for HMDB0014858 (Clodronate)

3D-SDF for HMDB0014858 (Clodronate)

PDB for HMDB0014858 (Clodronate)

3D PDB for HMDB0014858 (Clodronate)

SMILES for HMDB0014858 (Clodronate)

INCHI for HMDB0014858 (Clodronate)

Structure for HMDB0014858 (Clodronate)

3D Structure for HMDB0014858 (Clodronate)

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References