Computational Discovery of CDK8 Inhibitors From Natural Compounds in NPACT Database
Nguyen Xuan Ha1, Nguyen Van Trang2, Truong Thi Binh Giang3
1Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.
None:
Cyclin-dependent kinase 8 (CDK8) is a crucial transcriptional regulator and promising anticancer target. This study screened NPACT natural compounds to identify potential CDK8 inhibitors. Twenty-seven candidates showed strong binding (ΔG < -11 kcal/mol). Molecular dynamics confirmed stable complexes, with key interactions involving Asp173, Phe97, and Lys52. Steered MD revealed strong correlation with experimental affinities (R = -0.744). Compounds such as amentoflavone and artoindonesianin A showed higher pulling work than known inhibitors. Toxicity prediction indicated mostly low-to-moderate risk. These findings suggest that several natural compounds as promising CDK8 inhibitor leads, warranting further experimental validation.
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