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

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

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 7 , Issue 2 , 2007

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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.

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

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Article Details

VOLUME: 7
ISSUE: 2
Year: 2007
Page: [191 - 201]
Pages: 11
DOI: 10.2174/138955707779802598
Price: $58

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