Nilotinib

Nilotinib (AMN107, trade name Tasigna) is a tyrosine kinase inhibitor of Bcr-Abl, rationally designed to bind and inhibit the c-Abl kinase active site with more affinity than the prototypic Bcr-Abl kinase inhibitor Imatinib. Nilotinib inhibits the kinases Bcr-Abl, KIT, LCK, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11 and ZAK. Nilotinib possesses an in vitro Bcr-Abl binding potency 30 times greater than imatinib in imatinib-resistant cells, and 5-7 times greater than imatinib in imatinib-susceptible leukemic cells. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Nilotinib (AMN107) is more potent than imatinib against CML cells by a factor of 20 to 50.