Computational Design of Aminopyrimidine Derivatives with FDA-Approved Anticancer Drugs and their ADMET Pharmacokinetics and Molecular Docking Evaluation against Cancer-Inducing AXL Kinase Activity

Cancer is a global health hazard that is linked to one in six deaths worldwide. Treatment for cancer has always been fraught with difficulties. Keeping that, in mind, the present study deals with the design of aminopyrimidine derivatives with FDA-approved molecules as templates to evaluate their potential as anticancer agents against AXL tyrosine kinase receptor as the target protein through molecular docking and ADMET studies. Functions of the protein with respect to cancer are proliferation, survival, invasion, and migration of cancer cells, and inhibiting this enzyme helps in the development of medication against cancer. Molecular docking results reveal that among the 11 tested compounds, 03 compounds (i.e., exemestane, sonidegib, and vemurafenib) displayed docking scores of -10 kcal/mol, -12.3 kcal/mol, and -10 kcal/mol, respectively. Further, these designed compounds were subjected to ADMET tests such as oral rat acute toxicity (LD50), and results indicated that among 11 compounds tested, 03 compounds (i.e., exemestane, sonidegib, and vemurafenib) indicated less toxic effect with LD50 values of 2.996 mol/kg, 3.462 mol/kg, 3.303 mol/ kg within the accepted range. Further, these compounds could serve as potential lead compounds for the development of novel anticancer drugs through in-vitro and in-vivo analysis.