NCIt definition : The hydrochloride salt of nilotinib, an orally bioavailable aminopyrimidine-derivative
Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome
imatinib resistance, nilotinib binds to and stabilizes the inactive conformation of
the kinase domain of the Abl protein of the Bcr-Abl fusion protein, resulting in the
inhibition of the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive
(Ph ) chronic myeloid leukemia (CML) cells. This agent also inhibits the receptor
tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor
tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal
tumors (GISTs). With a binding mode that is energetically more favorable than that
of imatinib, nilotinib has been shown to have an approximately 20-fold increased potency
in kinase and proliferation assays compared to imatinib.;