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.