CP-609754 (LNK-754) 是一种有效且可逆的法尼基转移酶(farnesyltransferase) 抑制剂，具有潜在的抗癌活性。CP-609754 抑制重组人 H-Ras 和重组 K-Ras法尼基化的 IC50 分别为 0.57 ng/mL 和 46 ng/mL。
CP-609754 (LNK-754) is a potent and reversible farnesyltransferase inhibitor with potential anticancer activity.The IC50 for inhibiting farnesylation of recombinant human H-Ras is 0.57 ng/mL and recombinant K-Ras is 46 ng/mL[1].
CP-609754 (CP-609,754) is a reversible inhibitor of farnesyltransferase with a slow on/off rate. CP-609,754 inhibits farnesylation (IC50=1.72 ng/mL) of mutant H-Ras in 3T3 H-ras (61L)-transfected cell lines with SDS-PAGE analysis of [35S]methionine-labeled material[1].CP-609754 is competitive for the prenyl acceptor (H-Ras protein) and noncompetitive for the prenyl donor farnesyl PPI. CP-609754 interacts with the farnesyltransferase-farnesyl PPI complex and competes for the binding of the Ras protein. CP-609754 selectively inhibits farnesylation of both H- and K-Ras proteins in 3T3 transfectants[1].
CP-609754 (CP-609,754) has antitumor activity against 3T3 H-ras (61L) tumors in vivo[1].With twice daily oral dosing of CP-609754, tumor regression is achieved with a dose of 100 mg/kg; the ED50 for tumor growth inhibition is 28 mg/kg[1]. With continuous i.p. infusion of CP-609754, tumor growth is inhibited by >50%, and tumor farnesyltransferase activity inhibited by >30% in mice in which the plasma concentration of CP-609754 is maintained above 118 ng/mL[1].
[1]. Stacy L Moulder, et al. A 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.
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