Nilotinib

Chronic myelocytic leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl. Inhibitors of Bcr-Abl fusion protein, such as imatinib, have significantly improved patient care and produced remissions in all phases of CM L. However, imatinib resistance occurs in a significant number of patients, mainly through the development of mutations in the Bcr-Abl imatinib-binding domain. Nilotinib was developed in an attempt to circumvent resistance to imatinib. In preclinical and clinical investigations, efficacy of nilotinib has been observed in models of CML and other myeloproliferative disorders driven by Bcr-Abl and related kinases. In a phase II clinical trial of nilotinib in CML, major cytogenetic response rates were 52 and 33% for chronic- and accelerated-phase disease, respectively .... © 2008