Optimization of Benzoisothiazole dioxide inhibitory activity of the NS5B polymerase of HCV genotype 4 using ligand-steered homological modeling, reaction-driven scaffold-hopping and Enovo workflow.

Infection caused by hepatitis C virus (HCV) is a significant world health problem for which novel therapies are in urgent demand. The virus is highly prevalent in the Middle East and Africa particularly Egypt with more than 90% of infections due to genotype 4. Nonstructural (NS5B) viral proteins have emerged as an attractive target for HCV antivirals discovery.

New inhibitors of VEGFR-2 targeting the extracellular domain dimerization process.

We are reporting the discovery of small molecule inhibitors for vascular endothelial growth factor receptor type 2 (VEGFR-2) extracellular domain. The VEGFR-2 extracellular domain is responsible for the homo-dimerization process, which has been recently reported as a main step in VEGFR signal transduction cascade. This cascade is essential for the vascularization and survival of most types of cancers.