Exploring VEGFR2 as a Novel Target for Kidney Renal Clear Cell Carcinoma and Molecular Docking-Based Screening of Garcinia Oblongifolia Compounds

The increasing global cancer burden highlights the urgent need for effective cancer control strategies, particularly for aggressive types like Kidney Renal Clear Cell Carcinoma (KIRC). This study explores the potential of Garcinia oblongifolia compounds as targeted inhibitors of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a key player in tumor angiogenesis, using in silico approach for KIRC using computational approaches to assess their pharmacokinetic properties, toxicity profiles, and binding interactions. The role of VEGFR2 in cancer progression and its correlated genes were identified. A combination of ADMET profiling, bioactivity assessment, and molecular docking was utilized to screen the druglike compounds from G. oblongifolia. The study identifies three potential VEGFR2 inhibitors exhibiting a strong pharmacokinetic profile, binding affinity, and moderate bioactivity. The most promising compounds identified from G. oblongifolia are PubChem IDs: 11559542, 5280961, and 5281656 as promising VEGFR2 inhibitors with favorable docking energies and interactions with critical residues, including the DFG motif. Docking studies showed that 11559542's Pi-Anion interaction with ASP1046 stabilizes the DFG-out conformation, like Axitinib's hydrogen bonding. Compound PubChem ID:11559542 from G. oblongifolia, shows promising electrostatic interactions and moderate bioactivity, therefore, it can be considered a prime candidate for optimization to inhibit VEGFR2. The study supports targeted cancer therapy with natural product derivatives. However, in vitro and in vivo validation may be required in future studies.