Last Findings on Dual Inhibitors of Abl and Src Tyrosine-Kinases

Title: Last Findings on Dual Inhibitors of Abl and Src Tyrosine-Kinases

Volume: 7 Issue: 2

Author(s): S. Schenone, F. Manetti and M. Botta

Affiliation:

Keywords: Chronic myelogenous leukemia, tyrosine kinases, Src, Bcr-Abl, dual inhibitors, Imatinib, resistance

Abstract: Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome that expresses the constitutively activated tyrosine kinase Bcr-Abl; this enzyme causes hyperproliferation of the stem cells and the consequent pathology of the disease. Targeted inhibitors of Bcr-Abl have antiproliferative effects on the leukemic cells and induce apoptosis, favouring a regression of the CML chronic phase, but in the successive blast crisis phase cancer cells frequently develop resistance to Bcr-Abl inhibitors. Src is a family of nonreceptor tyrosine kinases, fundamental for cell development, growth, replication, adhesion, motility and is overexpressed in a wide number of human cancers. Recently it was demonstrated that Src is increased in hematopoietic cells expressing Bcr-Abl and is involved in the oncogenic pathway that causes CML. For this reason and also for the development of resistance to classical Bcr-Abl inhibitors, various dual Src/Abl inhibitors have been recently synthesized and tested. This mini review will be focused on the latest finding on this matter.

Cite this article as:

Schenone S., Manetti F. and Botta M., Last Findings on Dual Inhibitors of Abl and Src Tyrosine-Kinases, Mini-Reviews in Medicinal Chemistry 2007; 7 (2) . https://dx.doi.org/10.2174/138955707779802598