In-silico Exploration for Novel CDK8 Inhibitors: A Virtual Study by Pharmacophore Screening
Khushabu Patil, Mahesh Nemade, Anjali Prashant Bedse, Piyush Chandra, Rakesh Ranjan, Harshal L. Tare, Samir Patil · International Journal of Drug Delivery Technology · 2023
The primary goal of this research is to identify potent and safe CDK8 inhibitors from the ChEMBL (kinases) database. The study employs a multi-faceted computational approach to achieve its objectives. Structure-based pharmacophore modeling is used for the initial screening of potential CDK8 inhibitors. Subsequent molecular docking studies are conducted to assess the binding affinities of the screened molecules. Finally, toxicity profiling is carried out to ensure the safety of the potential inhibitors. A total of 150 molecules were identified that passed the initial pharmacophore screening. Among these, molecule CHEMBL404766 was found to have the highest binding affinity in molecular docking studies. Furthermore CHEMBL404766 was found to be the safest candidate, exhibiting a negligible toxic dose in toxicity profiling. The study suggests the potential use of computational approaches for the identification and design of potent and safe CDK8 inhibitors. These findings have significant implications for the development of targeted therapies in diseases where CDK8 plays a crucial role