T3DB: Etidronic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2009-07-30 17:58:40 UTC

Update Date

2014-12-24 20:26:07 UTC

Accession Number

T3D3483

Identification

Common Name

Etidronic acid

Class

Small Molecule

Description

Etidronic 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

MOL SDF PDB SMILES InChI

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 Formula

C₂H₈O₇P₂

Average Molecular Mass

206.028 g/mol

Monoisotopic Mass

205.975 g/mol

CAS Registry Number

7414-83-7

IUPAC Name

(1-hydroxy-1-phosphonoethyl)phosphonic acid

Traditional Name

etidronic acid

SMILES

CC(O)(P(O)(O)=O)P(O)(O)=O

InChI Identifier

InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)

InChI Key

InChIKey=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.

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
Organooxygen compound
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

1,1-bis(phosphonic acid) (CHEBI:4907 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Not Available

Chemical Roles

chelator

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	1.15e+01 g/L
LogP	-3.8

Predicted Properties

Property	Value	Source
Water Solubility	11.5 g/L	ALOGPS
logP	-0.77	ALOGPS
logP	-2.3	ChemAxon
logS	-1.2	ALOGPS
pKa (Strongest Acidic)	0.7	ChemAxon
pKa (Strongest Basic)	-5.1	ChemAxon
Physiological Charge	-3	ChemAxon
Hydrogen Acceptor Count	7	ChemAxon
Hydrogen Donor Count	5	ChemAxon
Polar Surface Area	135.29 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	34.51 m³·mol⁻¹	ChemAxon
Polarizability	13.97 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9310000000-2caef035e19867df64bf	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00di-9540000000-38ec250196bc1c488215	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-0090000000-a9f75f8364e22febc69e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-0190000000-7e7c121eec680994473e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-0390000000-f6ab7574deae5f44d8b4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-08j0-9620000000-0618a9cfbf1724258f3b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-03di-9100000000-cfaba7073e26e33fa329	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a6r-0960000000-dc95e917c594d7c69a00	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0560-6900000000-42d2a2563e015073e66b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9300000000-995ddbe23b852a05ae3b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udr-2980000000-d59d8cb7d24ab907283d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0fni-4920000000-15809f5e174b6322f374	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0059-9100000000-9b55901243a14d80a6f7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-1910000000-38d2c6a97af6630a8fa3	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-053r-9470000000-42c471e70e6c11b7b6d9	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9000000000-92dadebcb6c35ccc4a68	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0900000000-72d943e9ef38c579f95a	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03di-9200000000-57c7611567781ad9597a	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-03di-9000000000-fcbb693760d15d6e4929	2021-10-11	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum

Toxicity Profile

Route of Exposure

The amount of drug absorbed after an oral dose is approximately 3%.

Mechanism of Toxicity

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.

Metabolism

Not 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For 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 Level

Not Available

Health Effects

Not Available

Symptoms

Clinical 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.

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

4907

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Etidronic acid

PDB ID

911

ACToR ID

2607

Wikipedia Link

Etidronic_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.

MSDS

Link

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Hydroxylapatite

References

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 ]
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 ]
Ono K, Wada S: [Regulation of calcification by bisphosphonates]. Clin Calcium. 2004 Jun;14(6):60-3. [15577056 ]
Takaishi Y: [Treatment of periodontal disease, prevention and bisphosphonate]. Clin Calcium. 2003 Feb;13(2):173-6. [15775080 ]

Target Details

2. Receptor-type tyrosine-protein phosphatase S

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

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 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Target Details

3. V-type proton ATPase catalytic subunit A

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

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 ]

Target Details

4. Hydroxyapatite

Etidronic acid (T3D3483)

Structure for T3D3483: Etidronic acid

Targets

References

References

References