BMS-214662

BMS-214662 is a farnesyl transferase inhibitor. BMS-214662 can effectively block the localization and function of Ras protein in the cell membrane by inhibiting the pro-group modification of Ras protein, thereby exerting anti-tumor activity. BMS-214662 has an IC₅₀ value of 1.3 nM for H-Ras and 8.4 nM for K-Ras. BMS-214662 can be used to study Ras-related tumor diseases^[1][2]. IC50 & Target:IC50: 1.35 nM (farnesyl transferase), 1.3 μM (Ras-CVLL), 2.3 μM (K-Ras)^[1] In Vitro:BMS-214662 is over 1000-fold selective for farnesyl transferase, having IC₅₀ values for inhibition of geranylgeranylation of Ras-CVLL and K-Ras of 1.3 and 2.3 μM, respectively^[1]. BMS-214662 shows good potency in inhibiting H-ras-transformed rodent cells, A2780 human ovarian carcinoma tumor cells, and HCT-116 human colon carcinoma tumor cells. BMS-214662 is the most potent apoptotic FTI known and demonstrates broad spectrum yet robust cell-selective cytotoxic activity against a panel of cell lines with diverse histology^[2]. In Vivo:Tumors from BMS-214662-treated mice have increased numbers of apoptotic cells as compared with the nontreated control mice. The AIs in HCT-116 tumors are increased 4-10-fold in BMS-214662-treated mice as compared with nontreated controls. BMS-214662 is significantly cytotoxic to both HCT-116 and EJ-1 tumor cells; the doses of BMS-214662 required to kill 90% of clonogenic tumor cells are approximately 75 and 100 mg/kg for HCT-116 and EJ-1 tumors^[2].