Abstract Vascular Endothelial Growth Factor Receptor (VEGFR-2) is a tyrosine kinase receptor mainly known to be expressed in vascular endothelial cells. Overexpression of VEGFER-2 has been linked to tumor angiogenesis, necessitating the need for VEGFER-2 inhibitors. In-silico screening of oxa/thiazole carboxamide scaffold-bearing compounds retrieved from the ZINC database was conducted to identify potential anticancer agents with VEGFR-2 inhibitory effect. The interaction of VEGFR2 with tivozanib was used to generate a six-point pharmacophore model for screening ZINC chemical database. The virtual screening for potential VEGFR2 inhibitors generated 48 hits. The hits were filtered and ranked using molecular docking, drug-likeness, and absorption, distribution, metabolism, and excretion (ADME) protocols. The molecular docking results displayed ten compounds that adapted a similar binding mode and orientation within the active site of the VEGFR2 receptor. The molecular dynamic (MD) simulation analysis of the best hit, 3C, was carried out to validate the docking data. The RMSD and RMSF analysis was used to explain the stability of the VEGFR2 and 3c during the 50 ns simulation trajectory. The MD output revealed that the complex maintained conformational stability and consistent flexibility throughout the run. The results of the docking and simulation techniques supported each other. Thus, 3c emerged as a promising oxa/thiazole carboxamide-carrying lead molecule in our search for potential triple-negative breast cancer therapy. Citation Format: Steven M. Ewell, Getinet Mequanint, Donald Sikazwe, Kinfe Redda, Bereket Mochona. In-silico identification of oxa/thiazole carboxamides as potential breast cancer therapeutic agents with vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitory effect [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B005.