In search of novel inhibitors of anti-cancer drug target fibroblast growth factor receptors: Insights from virtual screening, molecular docking, and molecular dynamics

Abstract

Fibroblast growth factor receptors (FGFR) are an essential player in oncogenesis and tumor progression. LY2874455 was identified as a pan-FGFR inhibitor and has gone through phase I clinical trial. In the current study, virtual screening was conducted against the PubChem database using a pharmacophore model generated from the crystal structure of FGFR4 inhibited by LY2874455. PubChem 137300327 was identified as the most suitable compound from this screening. Later, molecular docking and molecular dynamics studies conducted with FGFRs corroborated the initial finding. Analysis of ADMET properties disclosed that LY2874455 and PubChem 137300327 share alike properties. Our study suggests that PubChem 137300327 is a potential pan-FGFR inhibitor and can be exploited to treat different cancers following validation in proper wet-lab experiments and study in animal cancer models. This compound also follows Lipinski’s rules and can be used as a lead compound to synthesize more effective anticancer compounds.