Identification of promising small-molecule inhibitors targeting STK17B for cancer therapeutics: molecular docking and molecular dynamics investigations

Abstract

Cancer is a complex disease characterized by the uncontrolled growth of abnormal cells, leading to the formation of tumours. STK17B, a member of the DAPK family, has been implicated in various cancers and is considered a potential therapeutic target. However, no drug in the market has been approved for the treatment of STK17 B-associated cancer disease. This research aimed to identify direct inhibitors of STK17B using computational techniques. Ligand-based virtual screening and molecular docking were performed, resulting in the selection of three lead compounds (CID_135698391, CID_135453100, CID_136599608) with superior binding affinities compared to the reference compound dovitinib. While molecular docking simulation revealed specific interactions between the lead compounds and key amino acid residues at the binding pocket of STK17B, molecular dynamics simulations demonstrated that CID_135453100 and CID_136599608 exhibit stable conformations and comparable flexibility to dovitinib. However, CID_135698391 did not perform well using this metric as it displayed poor stability. Overall, small-molecule compounds CID_135453100 and CID_136599608 showed promising binding interactions and stability, suggesting their potential as direct inhibitors of STK17B. These findings could contribute to the exploration of novel therapeutic options targeting STK17B in cancer treatment.