Clodronic Acid - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (4)Enzymes (1)

Targets (4)Enzymes (1)Biointeractions (2)

Identification

Name

Clodronic Acid

Accession Number

DB00720 (APRD00639)

Type

Small Molecule

Groups

Approved, Investigational, Vet Approved

Description

A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

(Dichloro-phosphono-methyl)-phosphonic acid

(Dichloromethylene)bisphosphonic acid

(Dichloromethylene)diphosphonic acid

Acide Clodronique

Acido Clodronico

Acidum Clodronicum

Clodronate

Clodronsaeure

Clodronsäure

Dichloromethanediphosphonic acid

Dichloromethylene-1,1-bisphosphonic acid

Dichloromethylene-1,1-diphosphonic acid

Dichloromethylidene diphosphonate

External IDs

BM 06.011

Product Ingredients

Ingredient	UNII	CAS	InChI Key	Details
Clodronate disodium	N030400H8J	88416-50-6	XWHPUCFOTRBMGS-UHFFFAOYSA-L	Details
Clodronate disodium tetrahydrate	Not Available	Not Available	Not applicable	Details

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Bonefos	Solution	60 mg	Intravenous	Bayer	1992-12-31	Not applicable	Canada
Bonefos	Capsule	400 mg	Oral	Bayer	1992-12-31	Not applicable	Canada
Clasteon	Capsule	400 mg	Oral	Sunovion	2004-05-13	Not applicable	Canada
Ostac Cap 400mg	Capsule	400 mg	Oral	Hoffmann La Roche	1994-12-31	2006-10-11	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Lodronat	Boehringer Ingelheim
Loron	Roche
Lytos	Roche
Ostac	Roche
Sindronat	Sindan

Brand mixtures

Not Available

Categories

UNII

0813BZ6866

CAS number

10596-23-3

Weight

Average: 244.892
Monoisotopic: 243.886016298

Chemical Formula

CH₄Cl₂O₆P₂

InChI Key

ACSIXWWBWUQEHA-UHFFFAOYSA-N

InChI

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

IUPAC Name

[dichloro(phosphono)methyl]phosphonic acid

SMILES

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

Pharmacology

Indication

For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.

Structured Indications

Pharmacodynamics

Clodronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and tiludronate. Clodronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the clodronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Clodronate has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.

Mechanism of action

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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
ADP/ATP translocase 1	Protein	yes	inhibitor	Human	P12235	details
ADP/ATP translocase 2	Protein	yes	inhibitor	Human	P05141	details
ADP/ATP translocase 3	Protein	yes	inhibitor	Human	P12236	details
Hydroxylapatite	Small molecule	yes	antagonist	Human	not applicable	details

Absorption

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

Volume of distribution

Not Available

Protein binding

2%-36%

Metabolism

Clodronate is not metabolized in humans.

Route of elimination

Not Available

Half life

Approximately 13 hours.

Clearance

Not Available

Toxicity

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.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Aceclofenac	The risk or severity of adverse effects can be increased when Aceclofenac is combined with Clodronate.	Approved
Acetylsalicylic acid	The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Clodronate.	Approved, Vet Approved
Aclarubicin	Aclarubicin may increase the hypocalcemic activities of Clodronate.	Investigational
Adapalene	The risk or severity of adverse effects can be increased when Adapalene is combined with Clodronate.	Approved
Aluminum hydroxide	The serum concentration of Clodronate can be decreased when it is combined with Aluminum hydroxide.	Approved
Amikacin	Amikacin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
Amrubicin	Amrubicin may increase the hypocalcemic activities of Clodronate.	Approved, Investigational
Andrographolide	The risk or severity of adverse effects can be increased when HMPL-004 is combined with Clodronate.	Investigational
Anisodamine	The risk or severity of adverse effects can be increased when Anisodamine is combined with Clodronate.	Investigational
Antipyrine	The risk or severity of adverse effects can be increased when Antipyrine is combined with Clodronate.	Approved
Apocynin	The risk or severity of adverse effects can be increased when Acetovanillone is combined with Clodronate.	Investigational
Apramycin	Apramycin may increase the hypocalcemic activities of Clodronate.	Experimental, Vet Approved
Apremilast	The risk or severity of adverse effects can be increased when Apremilast is combined with Clodronate.	Approved, Investigational
Arbekacin	Arbekacin may increase the hypocalcemic activities of Clodronate.	Approved
Azapropazone	The risk or severity of adverse effects can be increased when Azapropazone is combined with Clodronate.	Withdrawn
Azelastine	The risk or severity of adverse effects can be increased when Azelastine is combined with Clodronate.	Approved
Balsalazide	The risk or severity of adverse effects can be increased when Balsalazide is combined with Clodronate.	Approved, Investigational
Benoxaprofen	The risk or severity of adverse effects can be increased when Benoxaprofen is combined with Clodronate.	Withdrawn
Betulinic Acid	The risk or severity of adverse effects can be increased when Betulinic Acid is combined with Clodronate.	Investigational
Bismuth Subcitrate	The serum concentration of Clodronate can be decreased when it is combined with Bismuth Subcitrate.	Approved
Bromfenac	The risk or severity of adverse effects can be increased when Bromfenac is combined with Clodronate.	Approved
Bucillamine	The risk or severity of adverse effects can be increased when Bucillamine is combined with Clodronate.	Investigational
Calcium	The serum concentration of Clodronate can be decreased when it is combined with Calcium.	Nutraceutical
Calcium Acetate	The serum concentration of Clodronate can be decreased when it is combined with Calcium Acetate.	Approved
Calcium Carbonate	The serum concentration of Clodronate can be decreased when it is combined with Calcium carbonate.	Approved
Calcium Chloride	The serum concentration of Clodronate can be decreased when it is combined with Calcium Chloride.	Approved
Calcium Citrate	The serum concentration of Clodronate can be decreased when it is combined with Calcium citrate.	Approved
Calcium glubionate	The serum concentration of Clodronate can be decreased when it is combined with Calcium glubionate.	Approved
Calcium Gluceptate	The serum concentration of Clodronate can be decreased when it is combined with Calcium Gluceptate.	Approved
Calcium gluconate	The serum concentration of Clodronate can be decreased when it is combined with Calcium gluconate.	Approved, Vet Approved
Carprofen	The risk or severity of adverse effects can be increased when Carprofen is combined with Clodronate.	Approved, Vet Approved, Withdrawn
Castanospermine	The risk or severity of adverse effects can be increased when Castanospermine is combined with Clodronate.	Experimental
Celecoxib	The risk or severity of adverse effects can be increased when Celecoxib is combined with Clodronate.	Approved, Investigational
Chloroquine	The risk or severity of adverse effects can be increased when Chloroquine is combined with Clodronate.	Approved, Vet Approved
Choline magnesium trisalicylate	The risk or severity of adverse effects can be increased when Trisalicylate-choline is combined with Clodronate.	Approved
Clonixin	The risk or severity of adverse effects can be increased when Clonixin is combined with Clodronate.	Approved
Curcumin	The risk or severity of adverse effects can be increased when Curcumin is combined with Clodronate.	Investigational
Daunorubicin	Daunorubicin may increase the hypocalcemic activities of Clodronate.	Approved
Deferasirox	The risk or severity of adverse effects can be increased when Clodronate is combined with Deferasirox.	Approved, Investigational
Dexlansoprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with TAK-390MR.	Approved
Diclofenac	The risk or severity of adverse effects can be increased when Diclofenac is combined with Clodronate.	Approved, Vet Approved
Diflunisal	The risk or severity of adverse effects can be increased when Diflunisal is combined with Clodronate.	Approved
Doxorubicin	Doxorubicin may increase the hypocalcemic activities of Clodronate.	Approved, Investigational
Droxicam	The risk or severity of adverse effects can be increased when Droxicam is combined with Clodronate.	Approved
Duvelisib	The risk or severity of adverse effects can be increased when Duvelisib is combined with Clodronate.	Investigational
E-6201	The risk or severity of adverse effects can be increased when E6201 is combined with Clodronate.	Investigational
Ebselen	The risk or severity of adverse effects can be increased when Ebselen is combined with Clodronate.	Investigational
Epirizole	The risk or severity of adverse effects can be increased when Epirizole is combined with Clodronate.	Approved
Epirubicin	Epirubicin may increase the hypocalcemic activities of Clodronate.	Approved
Esomeprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with Esomeprazole.	Approved, Investigational
Estramustine	The serum concentration of Estramustine can be increased when it is combined with Clodronate.	Approved
Etanercept	The risk or severity of adverse effects can be increased when Etanercept is combined with Clodronate.	Approved, Investigational
Etodolac	The risk or severity of adverse effects can be increased when Etodolac is combined with Clodronate.	Approved, Investigational, Vet Approved
Etofenamate	The risk or severity of adverse effects can be increased when Etofenamate is combined with Clodronate.	Approved
Etoricoxib	The risk or severity of adverse effects can be increased when Etoricoxib is combined with Clodronate.	Approved, Investigational
Fenbufen	The risk or severity of adverse effects can be increased when Fenbufen is combined with Clodronate.	Approved
Fenoprofen	The risk or severity of adverse effects can be increased when Fenoprofen is combined with Clodronate.	Approved
Ferric Citrate	The serum concentration of Clodronate can be decreased when it is combined with Ferric Citrate.	Approved
Floctafenine	The risk or severity of adverse effects can be increased when Floctafenine is combined with Clodronate.	Approved, Withdrawn
Flurbiprofen	The risk or severity of adverse effects can be increased when Flurbiprofen is combined with Clodronate.	Approved, Investigational
Framycetin	Framycetin may increase the hypocalcemic activities of Clodronate.	Approved
Geneticin	Geneticin may increase the hypocalcemic activities of Clodronate.	Experimental
Gentamicin	Gentamicin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
GENTAMICIN C1A	GENTAMICIN C1A may increase the hypocalcemic activities of Clodronate.	Experimental
Higenamine	The risk or severity of adverse effects can be increased when Higenamine is combined with Clodronate.	Investigational
Ibuprofen	The risk or severity of adverse effects can be increased when Ibuprofen is combined with Clodronate.	Approved
Ibuproxam	The risk or severity of adverse effects can be increased when Ibuproxam is combined with Clodronate.	Withdrawn
Icatibant	The risk or severity of adverse effects can be increased when Icatibant is combined with Clodronate.	Approved
Idarubicin	Idarubicin may increase the hypocalcemic activities of Clodronate.	Approved
Indomethacin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Clodronate.	Approved, Investigational
Indoprofen	The risk or severity of adverse effects can be increased when Indoprofen is combined with Clodronate.	Withdrawn
Iron saccharate	The serum concentration of Clodronate can be decreased when it is combined with Iron saccharate.	Approved
Isoxicam	The risk or severity of adverse effects can be increased when Isoxicam is combined with Clodronate.	Withdrawn
Kanamycin	Kanamycin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
Kebuzone	The risk or severity of adverse effects can be increased when Kebuzone is combined with Clodronate.	Experimental
Ketoprofen	The risk or severity of adverse effects can be increased when Ketoprofen is combined with Clodronate.	Approved, Vet Approved
Ketorolac	The risk or severity of adverse effects can be increased when Ketorolac is combined with Clodronate.	Approved
Lansoprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with Lansoprazole.	Approved, Investigational
Leflunomide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clodronate.	Approved, Investigational
Lisofylline	The risk or severity of adverse effects can be increased when Lisofylline is combined with Clodronate.	Investigational
Lornoxicam	The risk or severity of adverse effects can be increased when Lornoxicam is combined with Clodronate.	Approved
Loxoprofen	The risk or severity of adverse effects can be increased when Loxoprofen is combined with Clodronate.	Approved
Lumiracoxib	The risk or severity of adverse effects can be increased when Lumiracoxib is combined with Clodronate.	Approved, Investigational
Magnesium carbonate	The serum concentration of Clodronate can be decreased when it is combined with Magnesium carbonate.	Approved
Magnesium Hydroxide	The serum concentration of Clodronate can be decreased when it is combined with Magnesium hydroxide.	Approved
Magnesium oxide	The serum concentration of Clodronate can be decreased when it is combined with Magnesium oxide.	Approved
Magnesium salicylate	The serum concentration of Clodronate can be decreased when it is combined with Magnesium salicylate.	Approved
Magnesium Sulfate	The serum concentration of Clodronate can be decreased when it is combined with Magnesium Sulfate.	Approved, Vet Approved
Magnesium Trisilicate	The serum concentration of Clodronate can be decreased when it is combined with Magnesium Trisilicate.	Approved
Masoprocol	The risk or severity of adverse effects can be increased when Masoprocol is combined with Clodronate.	Approved
Meclofenamic acid	The risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Clodronate.	Approved, Vet Approved
Mefenamic acid	The risk or severity of adverse effects can be increased when Mefenamic acid is combined with Clodronate.	Approved
Meloxicam	The risk or severity of adverse effects can be increased when Meloxicam is combined with Clodronate.	Approved, Vet Approved
Mesalazine	The risk or severity of adverse effects can be increased when Mesalazine is combined with Clodronate.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Metamizole is combined with Clodronate.	Withdrawn
Metrizamide	Metrizamide may increase the hypocalcemic activities of Clodronate.	Approved
Mizoribine	The risk or severity of adverse effects can be increased when Mizoribine is combined with Clodronate.	Investigational
Mycophenolate mofetil	The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Clodronate.	Approved, Investigational
Mycophenolic acid	The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Clodronate.	Approved
Nabumetone	The risk or severity of adverse effects can be increased when Nabumetone is combined with Clodronate.	Approved
Nafamostat	The risk or severity of adverse effects can be increased when Nafamostat is combined with Clodronate.	Approved, Investigational
Naftifine	The risk or severity of adverse effects can be increased when Naftifine is combined with Clodronate.	Approved
Naproxen	The risk or severity of adverse effects can be increased when Naproxen is combined with Clodronate.	Approved, Vet Approved
NCX 4016	The risk or severity of adverse effects can be increased when NCX 4016 is combined with Clodronate.	Investigational
Neamine	Neamine may increase the hypocalcemic activities of Clodronate.	Experimental
Neomycin	Neomycin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
Nepafenac	The risk or severity of adverse effects can be increased when Nepafenac is combined with Clodronate.	Approved
Netilmicin	Netilmicin may increase the hypocalcemic activities of Clodronate.	Approved
Niflumic Acid	The risk or severity of adverse effects can be increased when Niflumic Acid is combined with Clodronate.	Approved
Nimesulide	The risk or severity of adverse effects can be increased when Nimesulide is combined with Clodronate.	Approved, Withdrawn
Nitroaspirin	The risk or severity of adverse effects can be increased when Nitroaspirin is combined with Clodronate.	Investigational
Olopatadine	The risk or severity of adverse effects can be increased when Olopatadine is combined with Clodronate.	Approved
Olsalazine	The risk or severity of adverse effects can be increased when Olsalazine is combined with Clodronate.	Approved
Omeprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with Omeprazole.	Approved, Investigational, Vet Approved
Oxaprozin	The risk or severity of adverse effects can be increased when Oxaprozin is combined with Clodronate.	Approved
Oxyphenbutazone	The risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Clodronate.	Withdrawn
Pantoprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with Pantoprazole.	Approved
Parecoxib	The risk or severity of adverse effects can be increased when Parecoxib is combined with Clodronate.	Approved
Paromomycin	Paromomycin may increase the hypocalcemic activities of Clodronate.	Approved, Investigational
Phenylbutazone	The risk or severity of adverse effects can be increased when Phenylbutazone is combined with Clodronate.	Approved, Vet Approved
Pimecrolimus	The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Clodronate.	Approved, Investigational
Pirarubicin	Pirarubicin may increase the hypocalcemic activities of Clodronate.	Investigational
Pirfenidone	The risk or severity of adverse effects can be increased when Pirfenidone is combined with Clodronate.	Investigational
Piroxicam	The risk or severity of adverse effects can be increased when Piroxicam is combined with Clodronate.	Approved, Investigational
Plicamycin	Plicamycin may increase the hypocalcemic activities of Clodronate.	Approved, Withdrawn
Propacetamol	The risk or severity of adverse effects can be increased when Propacetamol is combined with Clodronate.	Approved
PTC299	The risk or severity of adverse effects can be increased when PTC299 is combined with Clodronate.	Investigational
Puromycin	Puromycin may increase the hypocalcemic activities of Clodronate.	Experimental
Rabeprazole	The therapeutic efficacy of Clodronate can be decreased when used in combination with Rabeprazole.	Approved, Investigational
Resveratrol	The risk or severity of adverse effects can be increased when Resveratrol is combined with Clodronate.	Experimental, Investigational
Ribostamycin	Ribostamycin may increase the hypocalcemic activities of Clodronate.	Approved
Rofecoxib	The risk or severity of adverse effects can be increased when Rofecoxib is combined with Clodronate.	Investigational, Withdrawn
Salicylamide	The risk or severity of adverse effects can be increased when Salicylamide is combined with Clodronate.	Approved
Salicylic acid	The risk or severity of adverse effects can be increased when Salicylic acid is combined with Clodronate.	Approved, Vet Approved
Salsalate	The risk or severity of adverse effects can be increased when Salsalate is combined with Clodronate.	Approved
Sisomicin	Sisomicin may increase the hypocalcemic activities of Clodronate.	Investigational
SP1049C	SP1049C may increase the hypocalcemic activities of Clodronate.	Investigational
Spectinomycin	Spectinomycin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
SRT501	The risk or severity of adverse effects can be increased when SRT501 is combined with Clodronate.	Investigational
Streptomycin	Streptomycin may increase the hypocalcemic activities of Clodronate.	Approved, Vet Approved
Streptozocin	Streptozocin may increase the hypocalcemic activities of Clodronate.	Approved
Sulfasalazine	The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Clodronate.	Approved
Sulindac	The risk or severity of adverse effects can be increased when Sulindac is combined with Clodronate.	Approved
Suprofen	The risk or severity of adverse effects can be increased when Suprofen is combined with Clodronate.	Approved, Withdrawn
Tenoxicam	The risk or severity of adverse effects can be increased when Tenoxicam is combined with Clodronate.	Approved
Teriflunomide	The risk or severity of adverse effects can be increased when Teriflunomide is combined with Clodronate.	Approved
Tiaprofenic acid	The risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Clodronate.	Approved
Tinoridine	The risk or severity of adverse effects can be increased when Tinoridine is combined with Clodronate.	Investigational
Tobramycin	Tobramycin may increase the hypocalcemic activities of Clodronate.	Approved, Investigational
Tolfenamic Acid	The risk or severity of adverse effects can be increased when Tolfenamic Acid is combined with Clodronate.	Approved
Tolmetin	The risk or severity of adverse effects can be increased when Tolmetin is combined with Clodronate.	Approved
Tranilast	The risk or severity of adverse effects can be increased when Tranilast is combined with Clodronate.	Approved, Investigational
Valdecoxib	The risk or severity of adverse effects can be increased when Valdecoxib is combined with Clodronate.	Investigational, Withdrawn
Valrubicin	Valrubicin may increase the hypocalcemic activities of Clodronate.	Approved
Zaltoprofen	The risk or severity of adverse effects can be increased when Zaltoprofen is combined with Clodronate.	Approved
Zileuton	The risk or severity of adverse effects can be increased when Zileuton is combined with Clodronate.	Approved, Investigational, Withdrawn
Zomepirac	The risk or severity of adverse effects can be increased when Zomepirac is combined with Clodronate.	Withdrawn
Zorubicin	Zorubicin may increase the hypocalcemic activities of Clodronate.	Experimental

Food Interactions

Food decreases absorption. Take on an empty stomach.

References

Synthesis Reference

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

US4859472

General References

Not Available

External Links

Resource	Link
Human Metabolome Database (HMDB)	HMDB14858
PubChem Compound	25419
PubChem Substance	46508646
ChemSpider	23731
BindingDB	50216172
ChEBI	110423
ChEMBL	CHEMBL12318
Therapeutic Targets Database	DAP000564
PharmGKB	PA10239
Drug Product Database	925
Wikipedia	Clodronate

ATC Codes

M05BA02 — Clodronic acid

AHFS Codes

92:00.00

PDB Entries

Not Available

FDA label

Not Available

MSDS

Download (120 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Unknown Status	Treatment	Aseptic Loosening of the Hip Prosthesis	1
3	Active Not Recruiting	Treatment	Cancer, Breast	1
3	Active Not Recruiting	Treatment	Radiation Induced Brachial Plexopathy	1
3	Completed	Treatment	Cancer, Breast	1
3	Completed	Treatment	Malignant Neoplasm of Prostate / Pain / Quality of Life	1
3	Completed	Treatment	Postmenopausal Osteoporosis (PMO)	1
Not Available	Completed	Not Available	Bone Neoplasms	1
Not Available	Completed	Not Available	Multiple Myeloma (MM) / Neoplasms, Breast / Osteolysis / Prostatic Neoplasms	1
Not Available	Completed	Treatment	Bone destruction	1
Not Available	Withdrawn	Not Available	Cancer, Breast	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Capsule	Oral	400 mg
Solution	Intravenous	60 mg

Prices

Unit description	Cost	Unit
Bonefos 60 mg/ml	13.69USD	ml
Bonefos 400 mg Capsule	2.04USD	capsule
Clasteon 400 mg Capsule	1.36USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	250 °C	PhysProp
water solubility	395 mg/L	Not Available
logP	-2.4	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	7.47 mg/mL	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

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8406
Blood Brain Barrier	+	0.9481
Caco-2 permeable	-	0.8956
P-glycoprotein substrate	Non-substrate	0.8597
P-glycoprotein inhibitor I	Non-inhibitor	0.9701
P-glycoprotein inhibitor II	Non-inhibitor	0.9903
Renal organic cation transporter	Non-inhibitor	0.958
CYP450 2C9 substrate	Non-substrate	0.7693
CYP450 2D6 substrate	Non-substrate	0.8234
CYP450 3A4 substrate	Non-substrate	0.697
CYP450 1A2 substrate	Non-inhibitor	0.8539
CYP450 2C9 inhibitor	Non-inhibitor	0.8878
CYP450 2D6 inhibitor	Non-inhibitor	0.9091
CYP450 2C19 inhibitor	Non-inhibitor	0.8449
CYP450 3A4 inhibitor	Non-inhibitor	0.9061
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9743
Ames test	Non AMES toxic	0.7328
Carcinogenicity	Carcinogens	0.6575
Biodegradation	Not ready biodegradable	0.927
Rat acute toxicity	2.6142 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9321
hERG inhibition (predictor II)	Non-inhibitor	0.9427

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

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

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organic acids and derivatives

Sub Class

Organic phosphonic acids and derivatives

Direct Parent

Bisphosphonates

Alternative Parents

Organic phosphonic acids / Organopnictogen compounds / Organophosphorus compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Alkyl chlorides

Substituents

Bisphosphonate / Organophosphonic acid / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organophosphorus compound / Organochloride / Organohalogen compound / Alkyl halide

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

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

Targets

Details

1. ADP/ATP translocase 1

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: inhibitor

General Function:: Adenine transmembrane transporter activity
Specific Function:: Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane.
Gene Name:: SLC25A4
Uniprot ID:: P12235
Molecular Weight:: 33064.265 Da

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 ]

Details

2. ADP/ATP translocase 2

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: inhibitor

General Function:: Ubiquitin protein ligase binding
Specific Function:: Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane. As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation.
Gene Name:: SLC25A5
Uniprot ID:: P05141
Molecular Weight:: 32851.965 Da

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 ]

Details

3. ADP/ATP translocase 3

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: inhibitor

General Function:: Atp:adp antiporter activity
Specific Function:: Catalyzes the exchange of cytoplasmic ADP with mitochondrial 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:: 32866.025 Da

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 ]

Details

4. Hydroxylapatite

Kind: Small molecule
Organism: Human
Pharmacological action: yes
Actions: antagonist

References

Ganguli A, Steward C, Butler SL, Philips GJ, Meikle ST, Lloyd AW, Grant MH: Bacterial adhesion to bisphosphonate coated hydroxyapatite. J Mater Sci Mater Med. 2005 Apr;16(4):283-7. [PubMed:15803271 ]
Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206 ]

Enzymes

Details

1. Prostaglandin G/H synthase 2

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: inhibitor

General Function:: Prostaglandin-endoperoxide synthase activity
Specific Function:: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:: PTGS2
Uniprot ID:: P35354
Molecular Weight:: 68995.625 Da

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 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:52

Get DrugBank to go!

Structure for DB00720 (Clodronic Acid)

Targets

References

References

References

References

Enzymes

References