Lonafarnib

Lonafarnib (SCH 66336) is a selectively farnesyl protein transferase (FPT) inhibitor, inhibiting H-ras, K-ras-4B and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib (8 μM) suppresses PKB/Akt activity as well as the phosphorylation of the Akt substrates glycogen synthase kinase (GSK)-3β, forkhead transcription factor, and BAD in SqCC/Y1 cells. Lonafarnib induces a CCAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter, thus induces CHOP-dependent DR5 up-regulation.