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 hyper-proliferation 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.
Schenone, S., Manetti, F., Botta, M. (2007). Last findings on dual inhibitors of Abl and Src tyrosine-kinases. MINI-REVIEWS IN MEDICINAL CHEMISTRY, 7, 191-201 [10.2174/138955707779802598].
Last findings on dual inhibitors of Abl and Src tyrosine-kinases
MANETTI, FABRIZIO;BOTTA, MAURIZIO
2007-01-01
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 hyper-proliferation 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.File | Dimensione | Formato | |
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https://hdl.handle.net/11365/21028
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