Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDS00372

Target Information
NameFarnesyl pyrophosphate synthetase    
Type of targetSuccessful target    
SynonymsFPP synthase    
FPP synthetase    
FPPS    
FPS    
Farnesyl diphosphate synthase    
Farnesyl diphosphate synthetase    
Farnesyl pyrophosphate synthase    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1]
Chagas' disease
[ICD9: 086   ICD10: B57]
[2]
Hypercholesterolemia
[ICD9: 272.0   ICD10: E78.0]
[3]
Leishmania infections
[ICD9: 001-139, 296.0, 296.4, 296.6   ICD10: A00-B99, F30]
[4]
Myeloma disease
[ICD9: 203.0   ICD10: C90.0]
[5]
Osteoporosis, unspecified
[ICD9: 733.0   ICD10: M80-M81]
[6]
Skeletal disorders[7]
Toxoplasma infections
[ICD9: 001-139   ICD10: A00-B99]
[4]
Trypanosomatid infections
[ICD9: 001-139   ICD10: A00-B99]
[8][9][2]
Drug(s)AlendronateApprovedOsteoporosis and Paget's disease[10][4][11][6]
IbandronateApprovedOsteoporosis in post-menopausal women[12]
PamidronateApprovedHypercalcemia[13]
Pamidronate disodiumApprovedOsteoporosis[10]
RisedronateApprovedPaget's disease[9]
ZoledronateApprovedHypercalcemia[14]
Zoledronic acidApprovedPostmenopausal osteoporosis[15][16]
EC NumberEC 2.5.1.1
EC 2.5.1.10
PathwayBiosynthesis of steroids
Metabolic pathways
Terpenoid biosynthesis
UniProt IDP14324
Q86C09
PDB Structure1YQ7; 1YV5; 1ZW5; 2F7M; 3DYF; 3DYG; 3DYH; 3EFQ.    
FunctionCatalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.    
SequenceMPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAWHSARCWCQAWTEEPRA LCSSLRMNGDQNSDVYAQEKQDFVQHFSQIVRVLTEDEMGHPEIGDAIARLKEVLEYNAI GGKYNRGLTVVVAFRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDSSLTRRG QICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIELFLQSSYQTEIGQTLD LLTAPQGNVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHANAKKILLE MGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVVQCLQRATPEQYQILKENYGQKE AEKVARVKALYEELDLPAVFLQYEEDSYSHIMALIEQYAAPLPPAVFLGLARKIYKRRK
Target ValidationClick to Find Target Validation Information.    
Inhibitor (1-hydroxy-1-phosphono-heptyl)-phosphonic acid[17]
(biphenyl-3-ylamino)methylenediphosphonic acid[18]
1- (but-2-ylamino)ethyl 1,I-bisphosphonic acid[17]
1-[ (cyclohexylamino)ethyl]-1,1-bisphosphonicacid[17]
1-[ (n-but-1-ylamino)ethyl]-1,1-bisphosphonic acid[17]
1-[ (n-hex-1-ylamino)ethyl]-1,1-bisphosphonic acid[17]
1-[ (n-oct-1-ylamino)ethyl]-1,1-bisphosphonic acid[17]
1-[ (prop-1-ylamino)ethyl]-1,1-bisphosphonic acid[17]
1-[ (prop-2-ylamino)ethyl]-1,1-bisphosphonicacid[17]
1-[ (tert-butylamino)ethyl]-1,1-bisphosphonicacid[17]
Alendronate[10][4][11][6]
Bisphosphonates[2]
Bisphosphonates alendronate[2]
Dimethylallyl Diphosphate[19]
FARNESYL DIPHOSPHATE[19]
Farnesyl pyrophosphate[20]
GERANYLGERANYL DIPHOSPHATE[19]
Geranyl Diphosphate[21]
Homorisedronate[2]
ISOPENTENYL PYROPHOSPHATE[19]
Ibandronate[12]
Incadronate[11]
Isopentyl Pyrophosphate[21]
Minodronate[11]
NE-10575[22]
NE21650[23]
NERIDRONIC ACID[22]
Pamidronate[13]
Pamidronate disodium[10]
Piridronic acid[22]
RIS[4]
Risedronate[9]
YM-175[22]
Zoledronate[14]
Zoledronic acid[15][16]
[2- (6-Chloro-purin-9-yl)ethyl]-bisphosphonic acid[24]
[2- (Benzoimidazol-1-yl)ethyl]-bisphosphonic acid[24]
[2- (Imidazol-1-yl)ethyl]-bisphosphonic acid[24]
[2- (Imidazol-2-yl-thio)ethyl]-bisphosphonic acid[24]
[2- (Purin-9-yl)ethyl]-bisphosphonic acid[24]
[2- (Pyrazol-1-yl)ethyl]-bisphosphonic acid[24]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Cancer metastasis therapeutic targets and drug discovery: emerging small-molecule protein kinase inhibitors. Expert Opin Investig Drugs. 2004 Jan;13(1):1-19. To Reference
Ref 2Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J Biol Chem. 2001 Sep 7;276(36):33930-7. Epub 2001 Jul 2. To Reference
Ref 3Squalene epoxidase as hypocholesterolemic drug target revisited. Prog Lipid Res. 2003 Jan;42(1):37-50. To Reference
Ref 4In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob Agents Chemother. 2002 Mar;46(3):929-31. To Reference
Ref 5How myeloma cells escape bisphosphonate-mediated killing: development of specific resistance with preserved sensitivity to conventional chemotherapeutics. Br J Haematol. 2003 Jul;122(2):202-10. To Reference
Ref 6Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. To Reference
Ref 7Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun. 1999 Oct 14;264(1):108-11. To Reference
Ref 8Farnesyl pyrophosphate synthase is an essential enzyme in Trypanosoma brucei. In vitro RNA interference and in vivo inhibition studies. J Biol Chem. 2003 May 9;278(19):17075-83. Epub 2003 Mar 4. To Reference
Ref 9Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14. To Reference
Ref 10Nat Rev Drug Discov. 2003 Jan;2(1):38-51.Knockouts model the 100 best-selling drugs--will they model the next 100? To Reference
Ref 11Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42. To Reference
Ref 12Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. To Reference
Ref 13Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Aug 30. [Epub ahead of print] To Reference
Ref 14Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies. Bioorg Med Chem Lett. 2008 May 1;18(9):2878-82. Epub 2008 Apr 8. To Reference
Ref 15Pulse treatment with zoledronic acid causes sustained commitment of bone marrow derived mesenchymal stem cells for osteogenic differentiation. Bone. 2009 May;44(5):858-64. Epub 2009 Jan 23. To Reference
Ref 16Zoledronic acid - a multiplicity of anti-cancer action. Curr Med Chem. 2007;14(20):2126-35. To Reference
Ref 17Bioorg Med Chem. 2008 Mar 15;16(6):3283-90. Epub 2007 Dec 10.Synthesis and biological evaluation of 2-alkylaminoethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii targeting farnesyl diphosphate synthase. To Reference
Ref 18Bioorg Med Chem. 2008 Oct 1;16(19):8959-67. Epub 2008 Aug 27.Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3'-azido, 3'-deoxythymidine: a QSAR investigation. To Reference
Ref 19Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 20A quantitative structure-activity relationship and pharmacophore modeling investigation of aryl-X and heterocyclic bisphosphonates as bone resorption agents. J Med Chem. 2003 Jul 3;46(14):2932-44. To Reference
Ref 21Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 22J Med Chem. 2008 Apr 10;51(7):2187-95. Epub 2008 Mar 8.Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. To Reference
Ref 23Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. Biochem Biophys Res Commun. 2002 Jan 18;290(2):869-73. To Reference
Ref 24J Med Chem. 2008 Nov 13;51(21):6800-7. Epub 2008 Oct 21.Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism. To Reference



 

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