Clodronate (CED0002804)

Record Information

Version

1.0

Creation Date

2009-07-15 20:41:25 UTC

Update Date

2026-05-14 16:47:03 UTC

SynCED ID

CED0002804

Secondary Accession Numbers

CHEM002109
T3D2663

Identification

Common Name

Clodronate

Class

Small Molecule

Description

Clodronate belongs to the bisphosphonates, a subclass of organic phosphonic acids and derivatives within the organic compounds. It is an exogenous solid with the formula CH4Cl2O6P2 and an average molecular weight of 244.89 g/mol. This compound is used as a drug (PMC12709581 ), an antineoplastic agent (PMC12709581 ), and a bone density conservation agent (PMC12709581 ). It is administered via oral or intravenous exposure routes. Clodronate is used in the treatment of osteoporosis (PMC12709581 ), hypercalcemia (PMC12709581 ), and breast cancer (PMC4876469 , PMC4944913 ). Additionally, it is used to treat neuropathic pain (PMC7064532 ). It has demonstrated therapeutic effects on inflammation (PMC12682720 ), hypercalcemia (PMC5037694 ), pain (PMC9392978 ), and breast cancer (PMC3722725 , PMC4876469 ). The pharmacological action of clodronate on mineralized tissues, particularly bone, is explained by the strong binding of the bisphosphonate group to the bone mineral hydroxyapatite. While the exact mechanism of action is not known, clodronate does not inhibit protein isoprenylation but can be metabolized intracellularly to AppCCl2p, a $\beta$-$\gamma$-methylene (AppCp-type) analog of ATP that is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by AppCCl2p is a likely route for inhibiting bone resorption and causing osteoclast apoptosis. Recorded protein targets include ADP/ATP translocase 1 (SLC25A4), ADP/ATP translocase 2 (SLC25A5), ADP/ATP translocase 3 (SLC25A6), Tyrosine-protein phosphatase non-receptor type 1 (PTPN1), Stromelysin-1 (MMP3), Macrophage metalloelastase (MMP12), and 72 kDa type IV collagenase (MMP2). Clodronate also binds protein-tyrosine-phosphatase.

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

Applications

Biological Roles

analgesic (PMC7064532 , PMC11312912 )?
drug (PMC12709581 )?
prodrug (PMC1408082 )?
bone density conservation agent (PMC6452576 )?

Chemical Roles

Not Available

Organoleptic Effects

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	Yes	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	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-001i-9040000000-af3c2e18902e147f8d42	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0006-1190000000-c4ab9891e7e58566d92f	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-03ed-3940000000-c29d8ff76855c0aaef6c	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-001i-9000000000-01a0eea1cf84ed37407a	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-03dl-0950000000-1845236a124e15b5c59b	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-006x-1390000000-3ae475737e6b4b8c7664	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-9000000000-974168c5223d898e9a79	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000x-6090000000-8989f8d7643382de70bc	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-03di-2900000000-95542c15d3d7df8beff2	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-03ea-4900000000-e088c1d2fe760f01f20d	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00dl-0090000000-125baa903034088b47b6	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00fr-6590000000-8d753c1dbb524b991ddf	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00di-1090000000-29462d306ece6e9df24d	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
1584.0 Log mg/kg [890:2800]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

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.

Carcinogenicity (IARC Classification)

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

Minimum Risk Level

Not Available

Symptoms

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

Treatment

Not Available

Health Effects

Health Effect	Relationship	Direction	Description	Reference
arthritis	Not Available	Not Available	A disorder characterized by inflammation involving a joint. (NCI CTCAE)	PMC11970870
inflammation	Has Therapeutic Effect On	Not Available	Not Available	PMC12682720
breast cancer	Has Therapeutic Effect On	Not Available	A breast cancer that has material basis in abnormally proliferating cells derives from epithelial cells. (DO)	PMC3722725 , PMC4876469
breast cancer	Not Available	Not Available	A breast cancer that has material basis in abnormally proliferating cells derives from epithelial cells. (DO)	PMC4876469 , PMC4944913
breast cancer	Associated With?	increase	A breast cancer that has material basis in abnormally proliferating cells derives from epithelial cells. (DO)	PMC5349995
osteoporosis	Not Available	Not Available	A disorder characterized by reduced bone mass, with a decrease in cortical thickness and in the number and size of the trabeculae of cancellous bone (but normal chemical composition), resulting in increased fracture incidence. (NCI CTCAE)	PMC12709581 , PMC8074527
neuropathic pain	Not Available	Not Available	Not Available	PMC7064532
pain	Has Therapeutic Effect On	Not Available	A disorder characterized by the sensation of marked discomfort, distress or agony. (NCI CTCAE)	PMC9392978 , PMC9716295
pain	Not Available	Not Available	A disorder characterized by the sensation of marked discomfort, distress or agony. (NCI CTCAE)	PMC11312912
hypercalcemia	Not Available	Not Available	A disorder characterized by laboratory test results that indicate an elevation in the concentration of calcium (corrected for albumin) in blood. (NCI CTCAE)	PMC12709581 , PMC8074527
hypercalcemia	Has Therapeutic Effect On	Not Available	A disorder characterized by laboratory test results that indicate an elevation in the concentration of calcium (corrected for albumin) in blood. (NCI CTCAE)	PMC5037694
bone disease	Has Therapeutic Effect On	Not Available	Not Available	PMC7795460
pulmonary fibrosis	Not Available	Not Available	Not Available	PMC11193999
osteosarcoma	Has Therapeutic Effect On	Not Available	Not Available	PMC2729740
Cell Death	Associated With?	decrease	Not Available	PMC9825525
osteonecrosis of the jaw	Associated With?	Not Available	Not Available	PMC5037694
Death	Has Therapeutic Effect On	Not Available	Not Available	PMC4723380
bone fracture	Not Available	Not Available	Not Available	PMC4049725
Cell Survival	Associated With?	decrease	Not Available	PMC4260733
Bone pain	Has Therapeutic Effect On	Not Available	Not Available	PMC5037694
Back pain	Has Therapeutic Effect On	Not Available	Not Available	PMC9716295
lytic metastatic bone lesion	Has Therapeutic Effect On	Not Available	Not Available	PMC5070259 , PMC9716295
lytic metastatic bone lesion	Not Available	Not Available	Not Available	PMC8074527 , PMC8268474
Paget disease of bone	Not Available	Not Available	Not Available	PMC8166716
metastatic prostate carcinoma	Not Available	Not Available	Not Available	PMC3862314
plasma cell myeloma	Not Available	Not Available	Not Available	PMC12709581
mammary Paget's disease	Not Available	Not Available	Not Available	PMC12709581 , PMC12209688
Fractures, Spontaneous	Associated With?	Not Available	Not Available	PMC4944913
complex regional pain syndrome type 1	Not Available	Not Available	Not Available	PMC7427076

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000010	Insecticides?Insecticides are synthetic chemicals designed to control or eliminate insect pests that threaten crops and other agricultural products.	Agriculture & land management	PubChem
CEDs000367	Drugs for treatment of bone diseases?Drugs for the treatment of bone diseases, such as bisphosphonates and calcitonin, are synthetic chemicals designed to prevent bone loss and promote bone health.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000519	Electrodes?Electrodes, used in various electrical and electronic applications, can be a source of synthetic chemical contamination due to the materials from which they are constructed and the processes involved in their manufacturing.	Electrical & Electronic Equipment	PubChem
CEDs000524	Hybrid Capacitors?Hybrid capacitors are energy storage devices that combine the properties of electrolytic and supercapacitors, utilizing a combination of electrochemical principles to achieve higher energy density and power density.	Electrical & Electronic Equipment	PubChem
CEDs000530	Radio Transmission Systems?Radio transmission systems utilize a variety of synthetic chemicals in their manufacturing and maintenance processes.	Electrical & Electronic Equipment	PubChem
CEDs000537	Television Systems?Television systems can be a source of synthetic chemical contamination due to the various materials and components used in their manufacture and operation.	Electrical & Electronic Equipment	PubChem
CEDs000539	Video Games?Video games, through their production and disposal processes, can be a source of synthetic chemical contamination.	Electrical & Electronic Equipment	PubChem
CEDs000545	Food Preservation?Food preservation often involves the use of synthetic chemicals, such as preservatives, flavor enhancers, and color additives, to extend shelf life and enhance the sensory qualities of food products.	Food, food processing & cookware	PubChem
CEDs000555	Bleaching Agents?Bleaching agents are chemical substances used to whiten or lighten materials, often employed in various cleaning products for their stain removal and disinfecting properties.	Household cleaning & consumer products	PubChem
CEDs000569	Tobacco Smoke Filters?Tobacco smoke filters are designed to reduce the inhalation of harmful substances in cigarette smoke, including tar and other particulate matter.	Household cleaning & consumer products	PubChem
CEDs000578	Making Cigars?The process of making cigars involves several steps, including the cultivation of tobacco, fermentation, and the application of various additives to enhance flavor and preservation.	Industrial manufacturing & chemical processing	PubChem
CEDs000596	Acaricides?Acaricides are synthetic chemicals specifically designed to target and control mite populations that can damage crops and plants.	Agriculture & land management	PubChem
CEDs000600	Herbicides And Algicides?Herbicides and algicides are synthetic chemicals primarily used to control unwanted plants and algae in various environments.	Agriculture & land management	PubChem
CEDs000602	Molluscicides?Molluscicides are synthetic chemicals specifically designed to control and eliminate mollusks, such as snails and slugs, which can be detrimental to crops and agricultural productivity.	Agriculture & land management	PubChem
CEDs000603	Nematocides?Nematocides are synthetic chemicals specifically designed to control nematodes, which are microscopic roundworms that can cause significant damage to crops and plants.	Agriculture & land management	PubChem
CEDs000606	Plant Growth Regulators?Plant Growth Regulators (PGRs) are synthetic chemicals designed to influence the growth and development of plants.	Agriculture & land management	PubChem
CEDs000610	Aftersun Products?Aftersun products are designed to soothe and hydrate the skin after sun exposure, often containing various synthetic chemicals such as emollients, preservatives, and fragrances.	Personal care & cosmetics	PubChem
CEDs000611	Anti Perspirants Or Body Deoderants?Antiperspirants and body deodorants commonly contain synthetic chemicals such as aluminum compounds, parabens, and synthetic fragrances.	Personal care & cosmetics	PubChem
CEDs000617	Lip Care Products?Lip care products, including lipsticks, balms, and glosses, often contain a variety of synthetic chemicals such as parabens, phthalates, and synthetic fragrances.	Personal care & cosmetics	PubChem
CEDs000620	Card Games?Card games often utilize synthetic materials for playing cards and associated gaming equipment, which may contain various chemicals such as polyvinyl chloride (PVC), plastics, and dyes.	Recreation & sports surfaces	PubChem
CEDs000632	Apparel?Apparel production often involves the use of various synthetic chemicals, including dyes, finishing agents, and preservatives.	Textiles, leather & furnishings	PubChem
CEDs000642	Footwear?Footwear production often involves the use of various synthetic chemicals, such as adhesives, dyes, and treatments, which can contribute to environmental contamination.	Textiles, leather & furnishings	PubChem
CEDs000678	Nitrogenous Fertilisers?Nitrogenous fertilizers are synthetic chemical compounds primarily used to enhance plant growth by supplying essential nitrogen, a crucial nutrient for photosynthesis and protein synthesis.	Agriculture & land management	PubChem
CEDs000684	Cements?Cements are a composite material primarily used as a binding agent in construction applications, formed by the calcination of limestone and clay minerals at high temperatures.	Building & Construction	PubChem
CEDs000685	Ceramics?Ceramics can be a source of synthetic chemical contamination through various additives and processing agents used in their production.	Building & Construction	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem
CEDs000739	Inks?Inks are complex mixtures composed of pigments or dyes, solvents, resins, and additives used primarily for printing and writing applications.	Paper, pulp & fiber products	PubChem
CEDs000744	Water, Wastewater, & Sewage Treatment?Water, wastewater, and sewage treatment processes are critical for managing and mitigating pollutants in water systems.	Wastewater, sanitation & biosolids	PubChem
CEDs01079	Tablet	Healthcare, pharmaceuticals & veterinary products	PMC12709581 , PMC12709581
CEDs01081	Tablets	Healthcare, pharmaceuticals & veterinary products	PMC12709581 , PMC12709581

Pathways

0 pathwaysPathway Source: PathBank

No pathways found

No metabolic pathways have been associated with this synthetic chemical

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Tumor necrosis factor	P01375	Humans	Known	Not Available
Click to view 3D structure	Interleukin-6	P05231	Humans	Known	Not Available
Click to view 3D structure	Voltage-gated purine nucleotide uniporter SLC17A9	Q9BYT1	Humans	Known	Not Available
Click to view 3D structure	Matrix metalloproteinase-14	P50281	Humans	Known	Not Available
Click to view 3D structure	Type IV secretion-like conjugative transfer relaxase protein TraI	B1LRJ1	Escherichia coli (strain SMS-3-5 / SECEC)	Predicted (SEA)	Prediction Confidence Score 1.0 Applicability Domain 1.0 Statistical Significance 1.00e-05 Supporting Reference Compounds 1 E-value 0.0778492
Click to view 3D structure	Phosphoglycerate kinase	P00560	Saccharomyces cerevisiae S288c	Predicted (SEA)	Prediction Confidence Score 0.259 Applicability Domain 0.259 Low confidence Statistical Significance 7.00e-05 Supporting Reference Compounds 1 E-value 0.544945
Click to view 3D structure	Farnesyl pyrophosphate synthase	Q0GKD7	Leishmania donovani	Predicted (SEA)	Prediction Confidence Score 0.254 Applicability Domain 0.259 Low confidence Statistical Significance 0.0011 Supporting Reference Compounds 14 E-value 8.87481
Click to view 3D structure	Farnesyl pyrophosphate synthase	P14324	Humans	Predicted (SEA)	Prediction Confidence Score 0.254 Applicability Domain 0.259 Low confidence Statistical Significance 0.0015 Supporting Reference Compounds 22 E-value 11.7552
Click to view 3D structure	Geranylgeranyl pyrophosphate synthase	O95749	Humans	Predicted (SEA)	Prediction Confidence Score 0.25 Applicability Domain 0.259 Low confidence Statistical Significance 0.0012 Supporting Reference Compounds 15 E-value 9.6533
Click to view 3D structure	Isopentenyl-diphosphate Delta-isomerase 1	O35760	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.233 Applicability Domain 0.233 Low confidence Statistical Significance 1.80e-04 Supporting Reference Compounds 1 E-value 1.40129
Click to view 3D structure	Farnesyl pyrophosphate synthase	P05369	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.233 Applicability Domain 0.233 Low confidence Statistical Significance 1.80e-04 Supporting Reference Compounds 1 E-value 1.40129
Click to view 3D structure	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3	Q8WN95	Bos taurus	Predicted (SEA)	Prediction Confidence Score 0.217 Applicability Domain 0.217 Low confidence Statistical Significance 1.80e-04 Supporting Reference Compounds 1 E-value 1.40129
Click to view 3D structure	Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2	Q6P549	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.217 Applicability Domain 0.217 Low confidence Statistical Significance 2.20e-04 Supporting Reference Compounds 1 E-value 1.71268
Click to view 3D structure	Type II inositol 1,4,5-trisphosphate 5-phosphatase	P32019	Humans	Predicted (SEA)	Prediction Confidence Score 0.217 Applicability Domain 0.217 Low confidence Statistical Significance 2.20e-04 Supporting Reference Compounds 1 E-value 1.71268
Click to view 3D structure	Farnesyl pyrophosphate synthase	Q4QBL1	Leishmania major	Predicted (SEA)	Prediction Confidence Score 0.209 Applicability Domain 0.259 Low confidence Statistical Significance 3.20e-04 Supporting Reference Compounds 5 E-value 2.49118
Click to view 3D structure	Glutamine synthetase, chloroplastic	P25462	Zea mays	Predicted (SEA)	Prediction Confidence Score 0.2 Applicability Domain 0.2 Low confidence Statistical Significance 0.0023 Supporting Reference Compounds 1 E-value 17.6718
Click to view 3D structure	Inositol-trisphosphate 3-kinase A	P17105	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.2 Applicability Domain 0.2 Low confidence Statistical Significance 2.00e-04 Supporting Reference Compounds 1 E-value 1.55698
Click to view 3D structure	72 kDa type IV collagenase	P08253	Humans	Predicted (SEA)	Prediction Confidence Score 0.192 Applicability Domain 0.212 Low confidence Statistical Significance 0.6947 Supporting Reference Compounds 400 E-value 5408.26
Click to view 3D structure	Inositol polyphosphate-5-phosphatase A	Q14642	Humans	Predicted (SEA)	Prediction Confidence Score 0.192 Applicability Domain 0.217 Low confidence Statistical Significance 1.60e-04 Supporting Reference Compounds 2 E-value 1.24559
Click to view 3D structure	Carbonic anhydrase 9	Q16790	Humans	Predicted (SEA)	Prediction Confidence Score 0.189 Applicability Domain 0.212 Low confidence Statistical Significance 0.6405 Supporting Reference Compounds 372 E-value 4986.24
Click to view 3D structure	Carbonic anhydrase 12	O43570	Humans	Predicted (SEA)	Prediction Confidence Score 0.189 Applicability Domain 0.212 Low confidence Statistical Significance 0.6123 Supporting Reference Compounds 332 E-value 4766.55
Click to view 3D structure	Carbonic anhydrase 1	P00915	Humans	Predicted (SEA)	Prediction Confidence Score 0.189 Applicability Domain 0.212 Low confidence Statistical Significance 0.6489 Supporting Reference Compounds 407 E-value 5051.48
Click to view 3D structure	Fructose-bisphosphate aldolase class 2	P0AB71	Escherichia coli (strain K12)	Predicted (SEA)	Prediction Confidence Score 0.185 Applicability Domain 0.185 Low confidence Statistical Significance 0.0017 Supporting Reference Compounds 1 E-value 13.0787
Click to view 3D structure	Mandelate racemase	P11444	Pseudomonas putida	Predicted (SEA)	Prediction Confidence Score 0.185 Applicability Domain 0.185 Low confidence Statistical Significance 0.016 Supporting Reference Compounds 1 E-value 124.637
Click to view 3D structure	Caspase-3	P42574	Humans	Known	Not Available
Click to view 3D structure	Geranylgeranyl pyrophosphate synthase BTS1	Q12051	Saccharomyces cerevisiae S288c	Predicted (SEA)	Prediction Confidence Score 0.184 Applicability Domain 0.212 Low confidence Statistical Significance 0.0013 Supporting Reference Compounds 4 E-value 10.1982
Click to view 3D structure	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3	Q14573	Humans	Predicted (SEA)	Prediction Confidence Score 0.184 Applicability Domain 0.208 Low confidence Statistical Significance 3.10e-04 Supporting Reference Compounds 4 E-value 2.41333
Click to view 3D structure	Carbonic anhydrase 2	P00918	Humans	Predicted (SEA)	Prediction Confidence Score 0.184 Applicability Domain 0.212 Low confidence Statistical Significance 0.7587 Supporting Reference Compounds 472 E-value 5906.73
Click to view 3D structure	Type 1 InsP3 receptor isoform S2	P79248	Sus scrofa	Predicted (SEA)	Prediction Confidence Score 0.183 Applicability Domain 0.2 Low confidence Statistical Significance 2.30e-04 Supporting Reference Compounds 2 E-value 1.79053
Click to view 3D structure	Farnesyl diphosphate synthase	Q8WS26	Trypanosoma cruzi	Predicted (SEA)	Prediction Confidence Score 0.183 Applicability Domain 0.259 Low confidence Statistical Significance 0.0021 Supporting Reference Compounds 5 E-value 16.1926
Click to view 3D structure	ADP/ATP translocase 1	P12235	Humans	Known	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.
Click to view 3D structure	ADP/ATP translocase 2	P05141	Humans	Known	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.
Click to view 3D structure	ADP/ATP translocase 3	P12236	Humans	Known	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.
Click to view 3D structure	Tyrosine-protein phosphatase non-receptor type 1	P18031	Humans	Known	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.
Click to view 3D structure	72 kDa type IV collagenase	P08253	Humans	Known	Not Available
Click to view 3D structure	Macrophage metalloelastase	P39900	Humans	Known	Not Available
Click to view 3D structure	Stromelysin-1	P08254	Humans	Known	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

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [PubMed: 18048412]
Cancer Care (2009). Fact Sheet for Clodronate. - http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=10571
Drugs.com - http://www.drugs.com/mmx/clodronate-disodium.html
Drugs.com - http://www.drugs.com/cons/Clodronate.html

Clodronate (CED0002804)

Structure for CHEM002109: Clodronate

No pathways found

Structure