Hck inhibitors as potential therapeutic agents in cancer and HIV infection

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 polymn. More importantly from a medicinal chem. point of view, high levels of Hck are involved in chronic myeloid leukemia and other hematol. tumors. Furthermore, Hck activity has been assocd. 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 biol. activities connected with malignancies and HIV infection, many of which have been only recently reported, and presents an overview of the compds. endowed with Hck inhibitory activity, esp. focusing on the medicinal chem. aspect