What question did this study set out to answer?

The research aims to identify natural compounds as potential inhibitors for CDK8, a target in cancer treatment.

April 17, 2026Chemistry & Biodiversity0 citations

Computational Discovery of CDK8 Inhibitors From Natural Compounds in NPACT Database

NHNguyen Xuan Ha NTNguyen Van Trang TGTruong Thi Binh Giang

Key Points

The research aims to identify natural compounds as potential inhibitors for CDK8, a target in cancer treatment.
Screened NPACT natural compounds for CDK8 inhibition.
Evaluated binding affinities through calculations (ΔG values).
Conducted molecular dynamics simulations to assess complex stability.
Performed steered MD to correlate with experimental affinities.
Predicted toxicity levels of the identified inhibitors.
Identified 27 candidates with strong binding affinities (ΔG < -11 kcal/mol).
Validated stable interactions with Asp173, Phe97, and Lys52 in molecular dynamics.
Observed a significant correlation (R = -0.744) between computational and experimental data.
Highlighted amentoflavone and artoindonesianin A as promising candidates.
Predicted low-to-moderate toxicity for most compounds.

Abstract

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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