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.
Subject(s)
HIV Infections/drug therapy , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-hck/antagonists & inhibitors , Animals , Drug Discovery , HIV Infections/enzymology , Humans , Neoplasms/enzymology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-hck/chemistry , Proto-Oncogene Proteins c-hck/metabolismABSTRACT
Within the EURopean Illicit TRAfficking Countermeasures Kit (EURITRACK) project, the gamma-ray spectra produced in a series of materials by 14-MeV tagged-neutron beams have been collected in the inspection portal equipped with large volume NaI(Tl) detectors, in order to build a database of signatures for various elements: C, N, O, Na, Al, Si, Cl, K, Ca, Cr, Fe, Ni, Cu, Zn, Pb. The measured spectra have been compared with prediction from Monte Carlo simulations to verify the consistency of the relevant nuclear data inputs. This library of measured 14-MeV neutron-induced gamma-ray spectra is currently used in a data processing algorithm to unfold the energy spectra of the transported goods into elementary contributions, thus allowing material identification.
