Lonafarnib

Description: Lonafarnib (formerly SCH66336; SCH-66336; Sarasar), a tricyclic derivative of carboxamide, is a novel, orally bioavailable and highly potent FPTase (farnesyl protein transferase) inhibitor with potential anticancer activity. It inhibits H-ras, K-ras-4B and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM in cell-free assays, respectively. Lonafarnib binds to and inhibits farnesyl transferase enzyme, which is involved in the post-translational modification and activation of Ras proteins. Ras proteins participate in numerous signalling pathways (proliferation, cytoskeletal organization), and play an important role in oncogenesis. Mutated ras proteins have been found in a wide range of human cancers.

References: Cancer Res. 1998; 58(21):4947-56; Cancer Res. 2003; 63(16):4796-800; Cancer Res. 2001; 61(11):4425-31.