Computational identification of potential inhibitors targeting in colorectal cancer.

Despite improved treatment options, colorectal cancer (CRC) remains a huge public health concern with a significant impact on affected individuals. Cell cycle dysregulation and overexpression of certain regulators and checkpoint activators are important recurring events in the progression of cancer. Cyclin-dependent kinase 1 (CDK1), a key regulator of the cell cycle component central to the uncontrolled proliferation of malignant cells, has been reportedly implicated in CRC. This study aimed to identify CDK1 inhibitors with potential for clinical drug research in CRC. Ten thousand (10,000) naturally occurring compounds were evaluated for their inhibitory efficacies against CDK1 through molecular docking studies. The stability of the lead compounds in complex with CDK1 was evaluated using molecular dynamics simulation for one thousand (1,000) nanoseconds. The top-scoring candidates' ADME characteristics and drug-likeness were profiled using SwissADME. Four hit compounds, namely, spiraeoside, robinetin, 6-hydroxyluteolin, and quercetagetin were identified from molecular docking analysis to possess the least binding scores. Molecular dynamics simulation revealed that robinetin and 6-hydroxyluteolin complexes were stable within the binding pocket of the CDK1 protein. The findings from this study provide insight into novel candidates with specific inhibitory CDK1 activities that can be further investigated through animal testing, clinical trials, and drug development research for CRC treatment.