Discovery of Pyrazole-Based CDK8 Inhibitors Using High-Throughput Virtual Screening
نویسندگان
1 Department of Cell & Molecular Biology, Faculty of Life Sciences & Biotechnology, Shahid Beheshti University, Tehran, Iran
2 Department of Technology, Faculty of Chemistry, K. N. Toosi University, Tehran, Iran
3 Department of Technology, Faculty of Chemistry, K. N. Toosi University, Tehran, Iran
4 Department of Technology, Faculty of Chemistry, K. N. Toosi University, Tehran, Iran
doi
10.48309/chemm.2025.499884.1880چکیده
Cancer remains a global health challenge, driving extensive research to discover effective treatments. This study introduces a novel approach by employing High-Throughput Virtual Screening (HTVS) to identify new pyrazole-based inhibitors of CDK8, a key enzyme implicated in cancer progression. Using Schrödinger's Maestro software, two crystal structures of CDK8 and 12,606 pyrazole compounds were analysed. Through multiple stages of virtual and visual screening, seven type I and two type II inhibitors (tautomers) were identified. The ADME properties of these compounds were evaluated using the QikProp function, revealing favourable pharmacokinetic profiles. The novelty of this study lies in its focus on the pyrazole scaffold, which enhances binding interactions with CDK8, and its use of HTVS as a cost-effective and efficient alternative to traditional laboratory methods. This approach not only accelerates the discovery of potential anticancer agents, but also provides insights into the role of pyrazole in enzyme inhibition.
