Hck Inhibitors as Potential Therapeutic Agents in Cancer and HIV Infection

Author(s): F. Musumeci, S. Schenone, C. Brullo, A. Desogus, L. Botta, C. Tintori

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 13 , 2015

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Abstract:

Hematopoietic cell kinase (Hck) is a member of the Src-family of non-receptor tyrosine kinases, which plays many roles in signalling pathways involved in the regulation of cell processes. Hck is expressed in cells of hematopoietic origin, specifically myelomonocytic cells and B lymphocytes. It participates in phagocytosis, adhesion, migration, regulation of protrusion formation on cell membrane, lysosome exocytosis, podosome formation and actin polymerization. More importantly from a medicinal chemistry point of view, high levels of Hck are involved in chronic myeloid leukemia and other hematologic tumors. Furthermore, Hck activity has been associated with virus infections including HIV-1. In particular, Hck is activated by the HIV-1 accessory protein Nef, a multifunctional HIV-1 protein that accelerates progression to AIDS and enhances the infectivity of progeny viruses. Nef binding to Hck leads to kinase activation which is important in AIDS pathogenesis. For these reasons, Hck represents a potentially good therapeutic target for the treatment of both specific cancers and HIV infection. This article summarizes Hck biological activities connected with malignancies and HIV infection, many of which have been only recently reported, and presents an overview of the compounds endowed with Hck inhibitory activity, especially focusing on the medicinal chemistry aspect.

Keywords: AIDS, cancer, Hck, HIV, inhibitor, Nef, tyrosine kinase.

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Article Details

VOLUME: 22
ISSUE: 13
Year: 2015
Page: [1540 - 1564]
Pages: 25
DOI: 10.2174/0929867322666150209152057
Price: $65

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