| Autor: |
Debnath A; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India., Singh RK; Department of Dravyaguna, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Mazumder R; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India., Mazumder A; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India., Srivastava S; Bhaskaracharya College of Applied Sciences, University of Delhi, Delhi, India., Chaudhary H; School of Medical & Allied Sciences, K R Mangalam University, Gurugram, India., Mangal S; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India., Sanchitra J; Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India., Tyagi PK; Noida Institute of Engineering and Technology, Greater Noida, India., Kumar Singh S; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India., Singh AK; Department of Dravyaguna, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. |
| Abstrakt: |
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. Consequently, this research aims to identify effective CDK12 inhibitors using comprehensive 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, MD Simulation, and in-vitro studies MTT assay. The research conducted yielded one compound ZINC11784547 has demonstrated robust binding affinity, favorable ADME features, less toxicity, remarkable stability, and cytotoxic effect. The identified compound holds promise for promoting cancer cell death through CDK12 inhibition. |
