In-silico Study on Pharmacokinetic Properties and VEGFR-2 Binding of Quininib Through Molecular Docking

Cancer growth depends on both the physiological process of angiogenesis, supported by binding of the vascular endothelial growth factor (VEGF) to endothelial cells of blood vessels, and on the interaction of angiogenic growth factors with receptors on endothelial cells, which promote angiogenesis through signaling pathways. The purpose of this in-silico study was to compare the binding of the small molecule inhibitor quininib (QNB) to the VEGFR2 receptor with the binding of the standard anti-cancer drug axitinib using AutoDock 4.2 to predict and assess docking scores; and to categorize each compound's pharmacokinetic properties using the Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) online tool. The results presented here demonstrate that quininib is capable of binding to the areas of the VEGFR2 receptor corresponding to the following amino acids: LEU889, VAL898, VAL899, LEU1019, ASP1028, and ILE1044. These binding interactions involve primarily hydrophobic interactions, together with a hydrogen bond with ASP1046 and a docking score of -4.72 kcal/mol. In addition, it was found that QNB possesses a high level of gastrointestinal (GI) absorption and the ability to cross the Blood–Brain Barrier (BBB), as well as that it conforms to Lipinski's rule of five for oral administration. We can therefore conclude that quininib has the potential to inhibit angiogenesis, which could thereby suppress the growth of cancer cells by binding to VEGFR2; and that even though its inhibition of VEGFR2 is lower than that of axitinib, there is potential for QNB to be developed as an orally administered agent following appropriate formulation and subsequent validation by further in-vitro and in-vivo studies.