Target Information

Target General Infomation
Target ID
T36098
Former ID
TTDS00372
Target Name
Farnesyl pyrophosphatesynthetase
Synonyms
FPP synthase; FPP synthetase; FPPS; FPS; Farnesyl diphosphate synthase; Farnesyl diphosphate synthetase; Farnesyl pyrophosphatesynthase
Target Type
Successful
Disease Bone disease [ICD10: M00-M99]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Hypercalcemia [ICD9: 275.42; ICD10: E83.5]
Osteoporosis [ICD9: 733.0, V07.4; ICD10: M80-M81, Z79.890]
Paget's disease [ICD9: 731; ICD10: M88]
Function
Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.
BioChemical Class
Alkyl aryl transferase
Target Validation
T36098
EC Number
EC 2.5.1.1
Drugs and Mode of Action
Drug(s) Incadronate Drug Info Approved Hypercalcemia [551871]
Minodronate Drug Info Approved Osteoporosis [546292], [551871]
NERIDRONIC ACID Drug Info Approved Bone disease [551871]
Pamidronate Drug Info Approved Hypercalcemia [536957], [542277]
Risedronate Drug Info Approved Paget's disease [537304], [540158]
Inhibitor (1-hydroxy-1-phosphono-heptyl)-phosphonic acid Drug Info [529229]
(biphenyl-3-ylamino)methylenediphosphonic acid Drug Info [529690]
1-(but-2-ylamino)ethyl 1,I-bisphosphonic acid Drug Info [529229]
1-[(cyclohexylamino)ethyl]-1,1-bisphosphonicacid Drug Info [529229]
1-[(n-but-1-ylamino)ethyl]-1,1-bisphosphonic acid Drug Info [529229]
1-[(n-hex-1-ylamino)ethyl]-1,1-bisphosphonic acid Drug Info [529229]
1-[(n-oct-1-ylamino)ethyl]-1,1-bisphosphonic acid Drug Info [529229]
1-[(prop-1-ylamino)ethyl]-1,1-bisphosphonic acid Drug Info [529229]
1-[(prop-2-ylamino)ethyl]-1,1-bisphosphonicacid Drug Info [529229]
1-[(tert-butylamino)ethyl]-1,1-bisphosphonicacid Drug Info [529229]
Bisphosphonates Drug Info [535202]
compound 2 Drug Info [529334]
compound 31 Drug Info [529121]
compound 5e Drug Info [529126]
Dimethylallyl Diphosphate Drug Info [551374]
diphosphoric acid Drug Info [529362]
Geranyl Diphosphate Drug Info [551393]
GERANYLGERANYL DIPHOSPHATE Drug Info [551374]
Homorisedronate Drug Info [535202]
Incadronate Drug Info [535102]
ISOPENTENYL PYROPHOSPHATE Drug Info [551374]
Isopentyl Pyrophosphate Drug Info [551393]
Minodronate Drug Info [535102]
minodronic acid Drug Info [530855]
NE-10575 Drug Info [529362]
NE10790 Drug Info [529362]
NE11808 Drug Info [529362]
NE21650 Drug Info [535340]
NE58018 Drug Info [529362]
NE58027 Drug Info [529362]
NE58043 Drug Info [529362]
NE58062 Drug Info [529362]
NE97220 Drug Info [529362]
NERIDRONIC ACID Drug Info [529362]
Pamidronate Drug Info [536847]
Piridronic acid Drug Info [529362]
RIS Drug Info [535372]
Risedronate Drug Info [535496]
[2-(6-Chloro-purin-9-yl)ethyl]-bisphosphonic acid Drug Info [529758]
[2-(Benzoimidazol-1-yl)ethyl]-bisphosphonic acid Drug Info [529758]
[2-(Imidazol-1-yl)ethyl]-bisphosphonic acid Drug Info [529758]
[2-(Imidazol-2-yl-thio)ethyl]-bisphosphonic acid Drug Info [529758]
[2-(Purin-9-yl)ethyl]-bisphosphonic acid Drug Info [529758]
[2-(Pyrazol-1-yl)ethyl]-bisphosphonic acid Drug Info [529758]
Pathways
KEGG Pathway Terpenoid backbone biosynthesis
Metabolic pathways
Biosynthesis of antibiotics
Influenza A
HTLV-I infection
PathWhiz Pathway Steroid Biosynthesis
Reactome Cholesterol biosynthesis
Activation of gene expression by SREBF (SREBP)
WikiPathways Activation of Gene Expression by SREBP (SREBF)
SREBP signalling
Cholesterol Biosynthesis
References
Ref 536957Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
Ref 537304Risedronate for treatment of osteoporosis. Nippon Rinsho. 2009 May;67(5):948-53.
Ref 540158(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3176).
Ref 542277(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7259).
Ref 546292Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007280)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 529121Activity of sulfonium bisphosphonates on tumor cell lines. J Med Chem. 2007 Nov 29;50(24):6067-79. Epub 2007 Oct 27.
Ref 529126Synthesis and biological evaluation of alpha-halogenated bisphosphonate and phosphonocarboxylate analogues of risedronate. J Med Chem. 2007 Nov 29;50(24):5967-75. Epub 2007 Nov 2.
Ref 529229Bioorg 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.
Ref 529334Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): tetramic, tetronic acids and dihydropyridin-2-ones. Bioorg Med Chem Lett.2008 Mar 15;18(6):1840-4.
Ref 529362J 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.
Ref 529690Bioorg 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.
Ref 529758J 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.
Ref 530855Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid. J Med Chem. 2010 May 13;53(9):3454-64.
Ref 535102Structure-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.
Ref 535202Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J Biol Chem. 2001 Sep 7;276(36):33930-7. Epub 2001 Jul 2.
Ref 535340Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. Biochem Biophys Res Commun. 2002 Jan 18;290(2):869-73.
Ref 535372In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob Agents Chemother. 2002 Mar;46(3):929-31.
Ref 535496Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14.
Ref 536847Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Aug 30.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.