Discovery of octahydropyrrolo [3,2‐b] pyridin derivative as a highly selective Type I inhibitor of FGFR3 over VEGFR2 by high‐throughput virtual screening

• Published in: Journal of cellular biochemistry Vol. 124; no. 2; pp. 221 - 238
• Main Authors: Wang, Xin, Ye, Cheng‐hao, Li, En‐min, Xu, Li‐yan, Lin, Wang‐qiang, Chen, Guang‐hui
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2023
• Subjects: Adenosine Triphosphate; Antineoplastic drugs; Antitumor agents; Binding; Carbonyl compounds; Carbonyls; Conformation; DFG‐in; Drug development; FGFR3; Fibroblast growth factor receptor 3; Fibroblast growth factor receptors; Free energy; Growth factors; Hydrogen bonds; Hydrophobicity; Inhibitors; Kinases; Ligands; ligand‐based pharmacophore; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; molecular dynamics simulations; Protein Kinase Inhibitors - pharmacology; Receptor, Fibroblast Growth Factor, Type 3 - metabolism; Receptors; Screening; selective inhibitor; Selectivity; Side effects; Steric hindrance; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGFR2; VEGFR2; molecular dynamics simulations; molecular docking; selective inhibitor; DFG-in; FGFR3; ligand-based pharmacophore

Although the aberrant activity of fibroblast growth factor receptor 3 (FGFR3) is implicated in various cancers, the reported kinase inhibitors of FGFR3 tend to cause side effects resulting from the inhibitory activity on vascular endothelial growth factor receptor 2 (VEGFR2). Therefore, it is necess...