Quest for Discovering Novel CDK12 Inhibitor by Leveraging High-Throughput Virtual Screening

Abstract CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology. Targeting CDK12 offers a promising strategy to develop therapy. Various monoclonal antibodies have drawn wide attention, but they are expensive compared to small-molecule inhibitors, limiting their accessibility and affordability for patients. Thus, in this research, we have tried to identify potent CDK12 inhibitors by employing extensive high-throughput virtual screening. RASPD protocol has been employed to screen three different databases against the target followed by drug-likeness, molecular docking, ADME, toxicity, Consensus molecular docking, and MD Simulation. The research conducted yielded one compound that have demonstrated robust binding affinity, favorable ADME features, little toxicity, and exceptional stability. The promotion of cancer cell death can be achieved by inhibiting CDK12 using this compound that have been identified.