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Background: VEGFR-2 tyrosine kinase inhibitors are receiving a lot of attention as prospective anticancer medications in the current drug discovery process., Objective: This work aims to explore the PubChem library for novel VEGFR-2 kinase inhibitors. 1H-Indazole-containing drug AXITINIB, or AG-013736 (FDA approved), is chosen as a rational molecule for drug design. This scaffold proved its efficiency in treating cancer and other diseases as well., Methods: The present study used the virtual screening of the database, protein preparation, grid creation, and molecular docking analyses., Results: The protein was validated on different parameters like the Ramachandran plot, the ERRAT score, and the ProSA score. The Ramachandran plot revealed that 92.1% of the amino acid residues were located in the most favorable region; this was complemented by an ERRAT score (overall quality factor) of 96.24 percent and a ProSA (Z score) of -9.24 percent. The Lipinski rule of five was used as an additional filter for screening molecules. The docking results showed values of binding affinity between -14.08 and -12.34 kcal/mol. The molecule C1 showed the highest docking value of -14.08 Kcal/mol with the maximum number of strong H-bonds by -NH of pyridine to amino acid Cys104 (4.22Å), -NH of indazole to Glu108 (4.72), and Glu70 to bridge H of -NH. These interactions are similar to Axitinib docking interactions like Glu70, Cys104, and Glu102. The docking studies revealed that pi-alkyl bonds are formed with unsubstituted pyridine, whereas important H-bonds are observed with different substitutions around -NH. Based on potential findings, we designed new molecules, and molecular docking studies were performed on the same protein along with ADMET studies. The designed molecules (M1-M4) also showed comparable docking results similar to Axitinib, along with a synthetic accessibility score of less than 4.5., Conclusion: The docking method employed in this work opens up new possibilities for the design and synthesis of novel compounds that can act as VEGFR-2 tyrosine kinase inhibitors and treat cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)