Ligand-Based Pharmacophore Screening Strategy: a Pragmatic Approach for Targeting HER Proteins.

摘要: Targeting ErbB family of receptors is an important therapeutic option, because its essential role in the broad spectrum human cancers, including non-small cell lung cancer (NSCLC). Therefore, present work, considerable effort has been made to develop inhibitor against HER proteins, by combining use pharmacophore modelling, docking scoring functions, and ADME property analysis. Initially, a five-point model was developed using known inhibitors. The generated then used as query screen total 468,880 compounds three databases namely ZINC, ASINEX, DrugBank. Subsequently, analysis carried out obtain hit molecules that could inhibit receptors. Further, GLIDE scores properties resulted one BAS01025917 with higher glide scores, increased CNS involvement, good pharmaceutically relevant than reference ligand, afatinib. Furthermore, inhibitory activity lead validated performing molecular dynamic simulations. Of note, found possess scaffolds antitumor activity. We believe this novel molecule can be further exploited for development pan-HER low toxicity greater potential.