SKI 606 Bosutinib SRC Inhibitors

Bosutinib, also known as SKI-606, is a synthetic quinolone derivative and dual kinase inhibitor that targets both Abl and Src kinases with potential antineoplastic activity. Unlike imatinib, bosutinib inhibits the autophosphorylation of both Abl and Src kinases, resulting in inhibition of cell growth and apoptosis. Because of the dual mechanism of action, this agent may have activity in resistant CML disease, other myeloid malignancies and solid tumors. Abl kinase is upregulated in the presence of the abnormal Bcr-abl fusion protein which is commonly associated with chronic myeloid leukemia (CML). Overexpression of specific Src kinases is also associated with the imatinib-resistant CML phenotype. Bosutinib received US FDA and EU European Medicines Agency approval on September 4, 2012 and 27 March, 2013 respectively for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.

Related Products:

Afatinib dimaleate; Neratinib; Bosutinib Intermediates; Bosutinib Monohydrate; Saracatinib; Dasatinib; NVP-BHG712; PP1; PP2; A-966492; G007-LK; SU6656; Tirbanibulin; TPX-0005; Afatinib

[1]. Boschelli DH, et al. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem, 2001, 44(23), 3965-3977.

[2]. Golas JM, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res, 2003, 63(2), 375-381.

[3]. Vultur A, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther, 2008, 7(5), 1185-1194.