Description
BMS 214662 is a potent inhibitor of farnesyltransferase (FTase; IC50 = 1.3 nM). It is selective for FTase over geranylgeranyl transferase (GGTase; IC50 = 1,900 nM). It inhibits the growth of MEK2, A2780, and PC3 cancer cells expressing wild-type Ras (IC50s = 2.5, 0.04, and 0.15 μM, respectively), as well as HCT116, MIP, RC-165, and MIA PaCa-2 cells expressing mutant K-Ras (IC50s = 0.06, 0.3, 0.3, and 0.12 μM, respectively). BMS 214662 induces apoptosis in HCT116 cells in a concentration-dependent manner. In vivo, BMS 214662 (600 mg/kg) is curative in an HCT116 mouse xenograft model. It also reduces tumor growth in Calu-1, HT-29, EJ-1, and MIA PaCa-2 mouse xenograft models.
Chemical Properties
Pale Yellow Solid
Uses
A potent and selective inhibitor of farnesyltransferase that induces mitochondrial apoptosis in chronic myeloid leukemia stem/progenitor cells, including CD34+38- cells, through activation of protein
kinase Cβ.
Definition
ChEBI: BMS-214662 is a member of the class of benzodiazepines that is 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine substituted by (1H-imidazol-5-yl)methyl, benzyl, (thiophen-2-yl)sulfonyl, and cyano groups at positions 1, 3R, 4 and 7, respectively. It is a potent inhibitor of farnesyltransferase (IC50 = 1.35nM) which was under clinical development for the treatment of solid tumors. It has a role as an antineoplastic agent, an apoptosis inducer and an EC 2.5.1.58 (protein farnesyltransferase) inhibitor. It is a member of imidazoles, a nitrile, a member of thiophenes, a sulfonamide, a member of benzenes and a benzodiazepine.
