In Silico Screening of 1,3,4-Thiadiazole Derivatives as Inhibitors of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2).

ABSTRACT: Angiogenesis plays a pivotal role in the growth, survival, and metastasis of solid tumors, with Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) being overexpressed in many human solid tumors, making it an appealing target for anti-cancer therapies. This study aimed to identify potential lead compounds with azole moiety exhibiting VEGFR-2 inhibitory effects. A ligand-based pharmacophore model was constructed using the X-ray crystallographic structure of VEGFR-2 complexed with tivozanib (PDB ID: 4ASE) to screen the ZINC15 database. Following virtual screening, six compounds demonstrated promising docking scores and drug-likeness comparable to tivozanib. These hits underwent detailed pharmacokinetic analysis to assess their absorption, distribution, metabolism, excretion, and toxicity

SUBMITTER: Ewell SM 

PROVIDER: S-EPMC11505934 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature