Target Information

Target General Infomation
Target ID
T52373
Former ID
TTDI00990
Target Name
Farnesyl pyrophosphate synthase
Gene Name
FDPS
Synonyms
(2E,6E)farnesyl diphosphate synthase; Dimethylallyltranstransferase; FPP synthase; FPS; Farnesyl diphosphate synthase; Geranyltranstransferase; FDPS
Target Type
Successful
Disease Bone resorption [ICD10: M80]
Hypercalcemia [ICD9: 275.42; ICD10: E83.5]
Osteoporosis in post-menopausal women [ICD9: 733; ICD10: M80-M81]
Osteoporosis; Paget's disease [ICD9: 731.0, 733.0; ICD10: M80-M81, 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
UniProt ID
P14324
EC Number
EC 2.5.1.1
Sequence
MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAWHSARCWCQAWTEEPRA
LCSSLRMNGDQNSDVYAQEKQDFVQHFSQIVRVLTEDEMGHPEIGDAIARLKEVLEYNAI
GGKYNRGLTVVVAFRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDSSLTRRG
QICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIELFLQSSYQTEIGQTLD
LLTAPQGNVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHANAKKILLE
MGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVVQCLQRATPEQYQILKENYGQKE
AEKVARVKALYEELDLPAVFLQYEEDSYSHIMALIEQYAAPLPPAVFLGLARKIYKRRK
Drugs and Mode of Action
Drug(s) Alendronate Drug Info Approved Osteoporosis; Paget's disease [536664], [540141]
Ibandronate Drug Info Approved Osteoporosis in post-menopausal women [537046], [540061]
Zoledronate Drug Info Approved Hypercalcemia [536957]
Modulator Alendronate Drug Info [556264]
Ibandronate Drug Info [556264]
OLPADRONIC ACID SODIUM SALT Drug Info [525426]
Zoledronate Drug Info [556264]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)
Superpathway of cholesterol biosynthesis
Trans, trans-farnesyl diphosphate biosynthesis
KEGG Pathway Terpenoid backbone biosynthesis
Metabolic pathways
Biosynthesis of antibiotics
Influenza A
HTLV-I infection
NetPath Pathway TCR Signaling Pathway
PANTHER Pathway Cholesterol biosynthesis
References
Ref 536664Osteonecrosis of the jaw. South Med J. 2008 Feb;101(2):160-5.
Ref 536957Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
Ref 537046Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009 Feb;122(2 Suppl):S14-21.
Ref 540061(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: 3059).
Ref 540141(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: 3141).
Ref 525426Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun. 1999 Feb 16;255(2):491-4.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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