An in silico approach for potential natural compounds as inhibitors of protein CDK1/Cks2

CDKs are pivotal mediators essential for the cellular cycle progression. CDKs have relatively constant levels, and their activity is regulated by cyclins, proteins whose concentrations fluctuate during each cell cycle. Consequently, more CDK family members were found that occupy crucial functions in a variety of processes. Moreover, CKS2 is a member of the CDK family, which has been implicated in several malignancies as an oncogene. Additionally, CKS2 is engaged in many biological processes, including the cell cycle transition. CKS2 may act synergistically to promote embryonic development and somatic cell division. Current CDK2 drugs, however, also suppress CDK1, posing a toxicity risk. Investigators demonstrated that the potential conformational maps of cyclin-free CDK1 and CDK2 exhibit slight but substantial differences. The CDK1 unique characteristics may be used to distinguish it from other CDKs in prospective cancer treatment design. Computational-based in silico docking investigations were performed to uncover promising CDK1/Cks2 (6GU7) inhibitors utilizing the Maestro tool. Curcumin, quercetin, withanolide, and genistein were selected against the protein CDK1/Cks2 for protein-ligand XP docking. The physicochemical, lipophilicity, water-solubility, pharmacokinetics, drug-likeness, medicinal chemistry, and toxicological properties were analyzed using SwissADME and pkCSM of the selected ligands. Curcumin exerted an excellent docking score complexed with 6GU7 compared to other ligands. The revealed hit may be a potent inhibitor of 6GU7. However, it will require to be assessed extensively in vivo and in vitro experimental models.