Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia

作者：Keller Gunhild; Schafhausen Philippe; Brummendorf Tim H^*

来源：Expert Review of Hematology, 2009, 2(5): 489-497.

DOI：10.1586/EHM.09.42

• BCR-ABL
• bosutinib
• CML
• dasatinib
• imatinib
• nilotinio
• point mutation
• SRC
• SRC/ABL kinase inhibitor
• tyrosine kinase

The tyrosine kinase inhibitor imatinib mesylate (IM) set new standards in the treatment of chronic myeloid leukemia (CML) However, emergence cif resistance to IM became a major therapeutic challenge Bosutinib (SKI-606) a 7-alkoxy-3-quinolinecarbonitrile, functions as a dual inhibitor of SRC and ABL kinases, and preclinical studies demonstrated a high antiproliferative activity in human and murine CML cell lines In ongoing Phase I/II clinical trials bosutinib yielded promising results revealing high clinical efficacy good tolerability and reduced toxicity in IM-resistant or -intolerant CML patients In this article we provide an overview on the mechanism of action and the preclinical and currently available clinical data for bosutinib Owing to its favorable toxicity profile and its high antileukemic activity, bosutinib is a promising novel treatment option for patients with CML A recently initiated randomized open-label Phase III clinical study will clarify its role in first-line therapy cf Philadelphia chromosome-positive chronic-phase CML

• 出版日期2009-10