Target Validation Information
TTD ID	T13127
Target Name	Farnesyl protein transferase (Ftase)
Type of Target	Successful
Drug Potency against Target		Drug Info	IC50 = 1.9 nM	[12]
		Drug Info	Ki = 0.93 nM	[13]
	AZD3409	Drug Info	IC50 = 3~14.2 nM	[14]
	Zarnestra	Drug Info	IC50 = 0.86 nM	[13]
		Drug Info	IC50 = 50 nM
		Drug Info	IC50 = 60 nM	[8]
		Drug Info	IC50 = 20 nM	[9]
	ABT-839	Drug Info	IC50 = 1.1 nM	[2]
	ACTINOPLANIC ACID A	Drug Info	IC50 = 230 nM	[8]
	BMS-404683	Drug Info	IC50 = 1.4 nM	[5]
	CLAVARINONE	Drug Info	IC50 = 8000 nM	[10]
	L-745631	Drug Info	IC50 = 10000 nM	[8]
	L-778123	Drug Info	IC50 = 98 nM	[4]
	MANUMYCIN A	Drug Info	IC50 = 11900 nM	[3]
	PB-27	Drug Info	IC50 = 2.8 nM	[5]
	PB-80	Drug Info	IC50 = 25 nM	[5]
	PB-81	Drug Info	IC50 = 1000 nM	[5]
	PD-83176	Drug Info	IC50 = 10 nM	[6]
	RPR-113829	Drug Info	IC50 = 17.5 nM	[7]
	RPR-114334	Drug Info	IC50 = 500 nM	[7]
	SCH-44342	Drug Info	IC50 = 250 nM	[1]
Action against Disease Model	Zarnestra	Drug Info	R115777 competitively inhibited the farnesylation of lamin B and K-RasB peptide substrates, with IC50s of 0.86 nM and 7.9 nM, respectively. In a panel of 53 h uMan t uMor cell lines tested for growth inhibition, approximately 75% were found to be sensitive to R115777. The majority of sensitive cell lines had a wild-type ras gene. T uMor cell lines bearing H-ras or N-ras mutations were among the most sensitive of the cell lines tested, with responses observed at nanomolar concentrations of R115777. T uMor cell lines bearing mutant K-ras genes required higher concentrations for inhibition of cell growth, with 50% of the cell lines resistant to R115777 up to concentrations of 500 nM. Inhibition of H-Ras, N-Ras, and lamin B protein processing was observed at concentrations of R115777 that inhibited cell proliferation	[11]
References
REF 1	Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.
REF 2	Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.
REF 3	A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
REF 4	Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I. Bioorg Med Chem Lett. 2004 Feb 9;14(3):639-43.
REF 5	Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J Med Chem. 2005 Jun 2;48(11):3704-13.
REF 6	Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J Med Chem. 1997 Jan 17;40(2):192-200.
REF 7	Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
REF 8	Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
REF 9	N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase. J Med Chem. 1998 Jul 2;41(14):2651-6.
REF 10	Clavaric acid and steroidal analogues as Ras- and FPP-directed inhibitors of human farnesyl-protein transferase. J Med Chem. 1998 Nov 5;41(23):4492-501.
REF 11	Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 2001 Jan 1;61(1):131-7.
REF 12	Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery, biology and clinical observations. Curr Top Med Chem. 2003;3(10):1103-14.
REF 13	Targeting the RAS signaling pathway in malignant hematologic diseases. Curr Drug Targets. 2007 Feb;8(2):217-35.
REF 14	Characterization of the in vitro activity of AZD3409, a novel prenyl transferase inhibitor. Cancer Chemother Pharmacol. 2011 Jan;67(1):137-45.

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