1.0 2009-07-15 20:41:25 UTC 2026-05-14 16:47:03 UTC T3D2663 Clodronate SmallMolecule 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. Drug Synthetic Toxin Organic Compound Organochloride Drug Antineoplastic Agent Antihypocalcemic Agent Bisphosphonate Bone Density Conservation Agent Osteoporosis Prophylactic Metabolite Synthetic Compound (Dichloro-phosphono-methyl)-phosphonic acid (Dichloromethylene)bisphosphonic acid (Dichloromethylene)diphosphonic acid Acide Clodronique Acido Clodronico Acidum Clodronicum Bonefos Clasteon Clodronic acid clodronic acid Clodronsaeure Clodronsäure Dichloromethanediphosphonic acid Dichloromethylene-1,1-bisphosphonic acid Dichloromethylene-1,1-diphosphonic acid Dichloromethylidene diphosphonate Lodronat Loron Lytos Ostac Sindronat CH4Cl2O6P2 244.892 243.886016298 [dichloro(phosphono)methyl]phosphonic acid clodronate 10596-23-3 OP(O)(=O)C(Cl)(Cl)P(O)(O)=O InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9) ACSIXWWBWUQEHA-UHFFFAOYSA-N Organic compounds Organic acids and derivatives Organic phosphonic acids and derivatives Bisphosphonates Bisphosphonates Alkyl chlorides Hydrocarbon derivatives Organic oxides Organic phosphonic acids Organochlorides Organophosphorus compounds Organopnictogen compounds Aliphatic acyclic compound Alkyl chloride Alkyl halide Bisphosphonate Hydrocarbon derivative Organic oxide Organic oxygen compound Organochloride Organohalogen compound Organophosphonic acid Organophosphorus compound Organopnictogen compound Aliphatic acyclic compounds 1,1-bis(phosphonic acid) one-carbon compound organochlorine compound Detected and Not Quantified Exogenous Cytoplasm Extracellular Membrane Solid White powder. melting_point 250°C solubility 395 mg/L logp -2.4 logp 0.16 ALOGPS logs -1.52 ALOGPS solubility 7.47e+00 g/l ALOGPS logp -0.067 ChemAxon pka_strongest_acidic 0.62 ChemAxon iupac [dichloro(phosphono)methyl]phosphonic acid ChemAxon average_mass 244.892 ChemAxon mono_mass 243.886016298 ChemAxon smiles OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ChemAxon formula CH4Cl2O6P2 ChemAxon inchi InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9) ChemAxon inchikey ACSIXWWBWUQEHA-UHFFFAOYSA-N ChemAxon polar_surface_area 115.06 ChemAxon refractivity 38.21 ChemAxon polarizability 15.3 ChemAxon rotatable_bond_count 2 ChemAxon acceptor_count 6 ChemAxon donor_count 4 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Oral, Intravenous. After oral administration, absorption is estimated at 1–3% of the ingested dose because of the low uptake from the gastrointestinal tract. 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. Clodronate is not metabolized in humans. It can be metabolized intracellularly to a beta-gamma-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Half Life: Approximately 13 hours. No indication of carcinogenicity to humans (not listed by IARC). A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors. #<HealthEffect::ActiveRecord_Associations_CollectionProxy:0x00007f722727f3d0> Signs and symptoms of hypocalcemia also may occur in some of these patients. DB00720 HMDB14858 25419 CHEMBL12318 23731 110423 Clodronic acid Clodronate 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 BE0000599 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. BE0000709 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. BE0000624 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. BE0004801 BE0000623 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. BE0000642 IC50 145 uM BindingDB 50216172 BE0001198 IC50 121 uM BindingDB 50216172 BE0001116 IC50 300 uM BindingDB 50216172 BE0004961 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.