Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDC00065

Target Information
NameFarnesyltransferase    
Type of targetDiscontinued target    
SynonymsCAAX farnesyltransferase    
CAAX farnesyltransferase alpha subunit    
FTase    
FTase-alpha    
GGTase-I-alpha    
Protein farnesyltransferase alpha subunit    
RAS proteins prenyltransferase    
RAS proteins prenyltransferase alpha    
Type I protein geranyl-geranyltransferase alpha subunit    
DiseaseAcute myeloid leukemia (AML)
[ICD9: 205.0   ICD10: C92.0]
[1][2][3]
Amebiasis
[ICD9: 006   ICD10: A06]
[4]
Bladder cancer
[ICD9: 188   ICD10: C67]
[5]
Breast cancer
[ICD9: 174, 175   ICD10: C50]
[6]
Cancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[7][8][9]
Colorectal Cancer
[ICD9: 153, 154   ICD10: C18-C21]
[1][2][3]
Malaria
[ICD9: 084   ICD10: B50-B54]
[10]
Non-small cell lung cancer (NSCLC)
[ICD9: 162   ICD10: C33, C34]
[11][12][13]
Pancreatic Cancer
[ICD9: 157   ICD10: C25]
[1][2][3]
Solid tumors
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[14][15][16]
Drug(s)AZD3409Discontinued in Phase ISolid Tumors[14][15][16]
BMS214662DiscontinuedCancer/Tumors[17][7][8][9][18]
CP-609,754Trial halted in Phase IBladder Cancer[5]
LonafarnibTerminated in Phase IIINon-small cell lung cancer[11][12][13]
ZarnestraDiscontinued in Phase IIPancreatic Cancer, Colorectal Cancer[1][2][3][19]
ZarnestraFDA non-approvable letterAcute myeloid leukemia[1][2][3][19]
BioChemical ClassTransferases transferring alkyl or aryl groups    
EC NumberEC 2.5.1.-
EC 2.5.1.58
EC 2.5.1.59
UniProt IDP49354
Q8IHP6
PDB Structure1JCQ; 1LD7; 1LD8; 1MZC; 1S63; 1SA4; 1TN6; 2F0Y; 2H6F; 2H6G; 2H6H; 2H6I; 2IEJ; 3E37.    
FunctionCatalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the c-terminus of several proteins having the c-terminal sequence cys-aliphatic-aliphatic-x.    
SequenceMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDS PSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLT RDAIELNAANYTVWHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLR DPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQR YFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNLLNQLL DLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEYWRYIG RSLQSKHSTENDSPTNVQQ
Related US Patent6,143,766
6,218,375
6,335,343
6,376,496
Target ValidationClick to Find Target Validation Information.    
Inhibitor (Z)-2-Methyl-3-tetradecyl-but-2-enedioic acid[20]
ABT-839[21]
ACTINOPLANIC ACID A[20]
ALPHA-HYDROXYFARNESYLPHOSPHONIC ACID[22]
AZD3409[14][15][16]
BMS-214662[23]
BMS-404683[24]
BMS214662[17][7][8][9][18]
CLAVARINONE[25]
CP-609,754[5]
FARNESYL[22]
FARNESYL DIPHOSPHATE[22]
GERANYLGERANYL DIPHOSPHATE[22]
L-731735[26]
L-745631[20]
L-778123[27]
Lonafarnib[11][12][13]
MANUMYCIN A[28]
PB-27[24]
PB-80[24]
PB-81[24]
PD-83176[29]
Pseudopeptide derivative[30]
Pseudopeptide derivative[30]
RPR-113829[31]
RPR-114334[31]
SCH-44342[32]
SCH66336[33]
Zarnestra[1][2][3][19]
BinderHuman PFT inhibitor[34]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15902-7. Epub 2008 Oct 6. To Reference
Ref 2The farnesyltransferase inhibitor R115777 (ZARNESTRA) enhances the pro-apoptotic activity of interferon-alpha through the inhibition of multiple survival pathways. Int J Cancer. 2007 Nov 15;121(10):2317-30. To Reference
Ref 3A phase I safety, pharmacological and biological study of the farnesyl protein transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors. Ann Oncol. 2006 Nov;17(11):1709-17. Epub 2006 Sep 15. To Reference
Ref 4Molecular cloning and characterization of a protein farnesyltransferase from the enteric protozoan parasite Entamoeba histolytica. J Biol Chem. 2004 Jan 16;279(3):2316-23. Epub 2003 Oct 28. To Reference
Ref 5A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors. Clin Cancer Res. 2004 Nov 1;10(21):7127-35. To Reference
Ref 6Farnesyltransferase inhibitors in breast cancer therapy. Cancer Invest. 2002;20 Suppl 2:30-7. To Reference
Ref 7Characterization of cancer stem cells in chronic myeloid leukaemia. Biochem Soc Trans. 2007 Nov;35(Pt 5):1347-51. To Reference
Ref 8Group IVC cytosolic phospholipase A2gamma is farnesylated and palmitoylated in mammalian cells. J Lipid Res. 2005 Oct;46(10):2122-33. Epub 2005 Aug 1. To Reference
Ref 9A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer. Clin Cancer Res. 2005 Mar 1;11(5):1877-83. To Reference
Ref 10Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity. Bioorg Med Chem Lett. 2001 Mar 26;11(6):761-4. To Reference
Ref 11The protein farnesyltransferase regulates HDAC6 activity in a microtubule-dependent manner. J Biol Chem. 2009 Apr 10;284(15):9648-55. Epub 2009 Feb 18. To Reference
Ref 12Combining the farnesyltransferase inhibitor lonafarnib with paclitaxel results in enhanced growth inhibitory effects on human ovarian cancer models in vitro and in vivo. Gynecol Oncol. 2008 Apr;109(1):97-106. Epub 2008 Jan 31. To Reference
Ref 13A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2008 Sep;62(4):631-46. Epub 2007 Dec 6. To Reference
Ref 14AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib. Breast Cancer Res Treat. 2007 May;102(3):275-82. Epub 2006 Sep 27. To Reference
Ref 15Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS mutated cell lines. Cancer Biol Ther. 2006 Sep;5(9):1206-10. Epub 2006 Sep 11. To Reference
Ref 16Quantification of farnesylmethylcysteine in lysates of peripheral blood mononuclear cells using liquid chromatography coupled with electrospray tandem mass spectrometry: pharmacodynamic assay for farnesyl transferase inhibitors. Anal Chem. 2006 Apr 15;78(8):2617-22. To Reference
Ref 17Mini Rev Med Chem. 2007 Nov;7(11):1108-19.Privileged structures: a useful concept for the rational design of new lead drug candidates. To Reference
Ref 18Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry. 2004 Jun 8;43(22):6877-84. To Reference
Ref 19Thiazolides: a new class of antiviral drugs. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):667-74. To Reference
Ref 20J Med Chem. 1997 Sep 12;40(19):2971-90.Ras farnesyltransferase: a new therapeutic target. To Reference
Ref 21Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. To Reference
Ref 22Berman 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 23J Med Chem. 2000 Oct 5;43(20):3587-95.Discovery of (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. To Reference
Ref 24J Med Chem. 2005 Jun 2;48(11):3704-13.Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. To Reference
Ref 25J Med Chem. 1998 Nov 5;41(23):4492-501.Clavaric acid and steroidal analogues as Ras- and FPP-directed inhibitors of human farnesyl-protein transferase. To Reference
Ref 26J Med Chem. 1998 Jul 2;41(14):2651-6.N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase. To Reference
Ref 27Bioorg Med Chem Lett. 2004 Feb 9;14(3):639-43.Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I. To Reference
Ref 28Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.A novel metal-chelating inhibitor of protein farnesyltransferase. To Reference
Ref 29J Med Chem. 1997 Jan 17;40(2):192-200.Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. To Reference
Ref 30Bioorg. Med. Chem. Lett. 5(22):2677-2682 (1995) To Reference
Ref 31J Med Chem. 1997 Jun 6;40(12):1763-7.Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. To Reference
Ref 32J Med Chem. 1999 Jun 17;42(12):2125-35.Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. To Reference
Ref 33Farnesyl transferase inhibitors as anticancer agents. Eur J Cancer. 2002 Sep;38(13):1685-700. To Reference
Ref 34Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40. To Reference



 

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