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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-12-07 02:50:07 UTC
HMDB IDHMDB0015265
Secondary Accession Numbers
  • HMDB15265
Metabolite Identification
Common NameTiludronate
DescriptionTiludronate is only found in individuals that have used or taken this drug. It is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. In vitro studies indicate that tiludronate acts primarily on bone through a mechanism that involves inhibition of osteoclastic activity with a probable reduction in the enzymatic and transport processes that lead to resorption of the mineralized matrix. Bone resorption occurs following recruitment, activation, and polarization of osteoclasts. Tiludronate appears to inhibit osteoclasts by at least two mechanisms: disruption of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus leading to detachment of osteoclasts from the bone surface and the inhibition of the osteoclastic proton pump.
Structure
Thumb
Synonyms
ValueSource
Tiludronate disodiumHMDB
Tiludronic acidHMDB
Tiludronic acid disodium saltHMDB
(chloro-4-Phenyl)thiomethylene biphosphonateMeSH
(chloro-4-Phenyl)thiomethylene bisphosphonateMeSH
SkelidMeSH
CL2SMBPMeSH
(4-Chlorophenyl)thiomethylene bisphosphonic acidMeSH
Chemical FormulaC7H9ClO6P2S
Average Molecular Weight318.608
Monoisotopic Molecular Weight317.928359441
IUPAC Name{[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid
Traditional Nametiludronate
CAS Registry Number89987-06-4
SMILES
OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O
InChI Identifier
InChI=1S/C7H9ClO6P2S/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14/h1-4,7H,(H2,9,10,11)(H2,12,13,14)
InChI KeyDKJJVAGXPKPDRL-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassOrganic phosphonic acids and derivatives
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Aryl thioether
  • Thiophenol ether
  • Chlorobenzene
  • Halobenzene
  • Alkylarylthioether
  • Benzenoid
  • Aryl chloride
  • Monocyclic benzene moiety
  • Aryl halide
  • Organophosphonic acid
  • Sulfenyl compound
  • Thioether
  • Organopnictogen compound
  • Organosulfur compound
  • Organophosphorus compound
  • Organochloride
  • Organohalogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility6.97 g/LNot Available
LogP-0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.97 g/LALOGPS
logP0.62ALOGPS
logP1.32ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)1.03ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.06 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity65.11 m³·mol⁻¹ChemAxon
Polarizability25.37 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00l6-9845000000-f6b7a670cc0b0a19c852View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0039000000-ab24506a08e68a6b0702View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0079-1190000000-187e9be9bae033802f81View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9320000000-3b1fcb1af6dc135e5934View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1093000000-d0499b987fed9300a204View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014r-0092000000-02dee9f83fd33c231117View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9460000000-fb9cbdc13ede2f2f0469View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01133 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01133 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01133
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID54905
KEGG Compound IDC08141
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTiludronate
METLIN IDNot Available
PubChem Compound60937
PDB IDNot Available
ChEBI ID399299
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T: A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995 Aug;17(2):137-44. [PubMed:8554921 ]
  2. Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. [PubMed:8573422 ]
  3. Rogers MJ: New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9(32):2643-58. [PubMed:14529538 ]

Enzymes

General function:
Involved in ATP binding
Specific function:
Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name:
ATP6V1A
Uniprot ID:
P38606
Molecular weight:
68303.5
References
  1. David P, Nguyen H, Barbier A, Baron R: The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996 Oct;11(10):1498-507. [PubMed:8889850 ]
General function:
Involved in phosphatase activity
Specific function:
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.
Gene Name:
PTPN1
Uniprot ID:
P18031
Molecular weight:
49966.44
References
  1. Murakami H, Takahashi N, Tanaka S, Nakamura I, Udagawa N, Nakajo S, Nakaya K, Abe M, Yuda Y, Konno F, Barbier A, Suda T: Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone. 1997 May;20(5):399-404. [PubMed:9145236 ]