Tipifarnib

Tipifarnib (trade name Zarnestra) is a potent and selective farnesyltransferase inhibitor with IC50 of 0.6 nM. Tipifarnib (R115777) inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis. Tipifarnib exerts selective in vitro toxicity against clonal MDS hematopoiesis at concentrations less than 10 nM the effect being more prominent in white cell progenitors. R115777 results in Ki-67 value of 67.3% in vivo.