Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:58:40 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3483
Identification
Common NameEtidronic acid
ClassSmall Molecule
DescriptionEtidronic acid is only found in individuals that have used or taken this drug. It is a diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover. [PubChem] Bisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone.
Compound Type
  • Antihypocalcemic Agent
  • Antineoplastic Agent
  • Bisphosphonate
  • Bone Density Conservation Agent
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Organic Compound
  • Osteoporosis Prophylactic
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(1-Hydroxyethylene)diphosphonic acid
(1-Hydroxyethylidene)bis(phosphonic acid)
(1-Hydroxyethylidene)bisphosphonic acid
(1-Hydroxyethylidene)diphosphonic acid
(Hydroxyethylidene)diphosphonic acid
1,1,1-Ethanetriol diphosphonate
1-Hydroxy-1,1-diphosphonoethane
1-hydroxyethane 1,1-diphosphonic acid
1-Hydroxyethane-1,1-bisphosphonic acid
1-Hydroxyethane-1,1-diphosphonate
1-Hydroxyethane-1,1-diphosphonic acid
1-Hydroxyethanediphosphonic acid
1-Hydroxyethylidene-1,1-bisphosphonate
1-Hydroxyethylidene-1,1-diphosphonic acid
Acetodiphosphonic acid
Acide etidronique
Acido etidronico
Acidum etidronicum
Didronel
EHDP
Ethane-1-hydroxy-1,1-bisphosphonic acid
Ethane-1-hydroxy-1,1-diphosphonate
Ethane-1-hydroxy-1,1-diphosphonic acid
Etidron
Etidronate
Etidronate Disodium
Etidronsaeure
Etidronsäure
HEDP
Hydroxyethanediphosphonic acid
Oxyethylidenediphosphonic acid
Chemical FormulaC2H8O7P2
Average Molecular Mass206.028 g/mol
Monoisotopic Mass205.975 g/mol
CAS Registry Number7414-83-7
IUPAC Name(1-hydroxy-1-phosphonoethyl)phosphonic acid
Traditional Nameetidronic acid
SMILESCC(O)(P(O)(O)=O)P(O)(O)=O
InChI IdentifierInChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)
InChI KeyInChIKey=DBVJJBKOTRCVKF-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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Organophosphonic acid
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organophosphorus compound
  • Organooxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.15e+01 g/L
LogP-3.8
Predicted Properties
PropertyValueSource
Water Solubility11.5 g/LALOGPS
logP-0.77ALOGPS
logP-2.3ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.7ChemAxon
pKa (Strongest Basic)-5.1ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area135.29 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity34.51 m³·mol⁻¹ChemAxon
Polarizability13.97 ųChemAxon
Number of Rings0ChemAxon
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, Positivesplash10-001i-9310000000-2caef035e19867df64bfView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9540000000-38ec250196bc1c488215View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0090000000-a9f75f8364e22febc69eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0190000000-7e7c121eec680994473eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0390000000-f6ab7574deae5f44d8b4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-08j0-9620000000-0618a9cfbf1724258f3bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03di-9100000000-cfaba7073e26e33fa329View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a6r-0960000000-dc95e917c594d7c69a00View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0560-6900000000-42d2a2563e015073e66bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9300000000-995ddbe23b852a05ae3bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udr-2980000000-d59d8cb7d24ab907283dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fni-4920000000-15809f5e174b6322f374View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0059-9100000000-9b55901243a14d80a6f7View in MoNA
Toxicity Profile
Route of ExposureThe amount of drug absorbed after an oral dose is approximately 3%.
Mechanism of ToxicityBisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone.
MetabolismNot metabolized. Route of Elimination: Etidronate disodium is not metabolized. Within 24 hours, approximately half the absorbed dose is excreted in urine; the remainder is distributed to bone compartments from which it is slowly eliminated. Unabsorbed drug is excreted intact in the feces. Half Life: In normal subjects, plasma half-life of etidronic acid, based on non-compartmental pharmacokinetics is 1 to 6 hours.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of symptomatic Paget's disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsClinical experience with acute etidronic acid overdosage is extremely limited. 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. Some patients may develop vomiting. In one event, an 18-year-old female who ingested an estimated single dose of 4800 to 6000 mg (67 to 100 mg/kg) of etidronate was reported to be mildly hypocalcemic (7 .5 2 mg/ dl) and experienced paresthesia of the fingers.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01077
HMDB IDHMDB15210
PubChem Compound ID3305
ChEMBL IDCHEMBL871
ChemSpider ID3189
KEGG IDC07736
UniProt IDNot Available
OMIM ID
ChEBI ID4907
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEtidronic acid
PDB ID911
ACToR ID2607
Wikipedia LinkEtidronic_acid
References
Synthesis Reference

Rogovin, L.,Brawn, D.P. and Kalberg, AN.; US. Patent 3,400,147; September 3,1968; assigned to The Procter & Gamble Co.

MSDSLink
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

References
  1. Grases F, Sanchis P, Perello J, Isern B, Prieto RM, Fernandez-Palomeque C, Torres JJ: Effect of crystallization inhibitors on vascular calcifications induced by vitamin D: a pilot study in Sprague-Dawley rats. Circ J. 2007 Jul;71(7):1152-6. [17587727 ]
  2. 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. [16046206 ]
  3. Ono K, Wada S: [Regulation of calcification by bisphosphonates]. Clin Calcium. 2004 Jun;14(6):60-3. [15577056 ]
  4. Takaishi Y: [Treatment of periodontal disease, prevention and bisphosphonate]. Clin Calcium. 2003 Feb;13(2):173-6. [15775080 ]
General Function:
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function:
Interacts with LAR-interacting protein LIP.1.
Gene Name:
PTPRS
Uniprot ID:
Q13332
Molecular Weight:
217039.825 Da
References
  1. Schmidt A, Rutledge SJ, Endo N, Opas EE, Tanaka H, Wesolowski G, Leu CT, Huang Z, Ramachandaran C, Rodan SB, Rodan GA: Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3068-73. [8610169 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Proton-transporting atpase activity, rotational mechanism
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 Da
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. [8889850 ]