azd4547 and Neoplasms

Alterations of fibroblast growth factor receptors (FGFRs) play key roles in numerous cancer progression and development, which makes FGFRs attractive targets in the cancer therapy. In the present study, based on a newly devised FGFR target-specific scoring function, a novel FGFR inhibitor hit was identified through virtual screening. Hit-to-lead optimization was then performed by integrating molecular docking and site-of-metabolism predictions with an array of in vitro evaluations and X-ray cocrystal structure determination, leading to a covalent FGFR inhibitor

Topics: Amino Acid Sequence; Drug Design; Drug Discovery; Humans; Kinetics; Molecular Docking Simulation; Molecular Structure; Molecular Targeted Therapy; Neoplasms; Phosphorylation; Protein Isoforms; Protein Kinase Inhibitors; Receptors, Fibroblast Growth Factor; Sequence Homology, Amino Acid; Structure-Activity Relationship