Identification of the Potential Pan-CDK Antagonists: Tracing the Path of Virtual Screening and Inhibitory Activity on Lung Cancer Cells

Overview

Journal Mol Divers

Date 2024 Jul 28

PMID 39069541

Authors

Jia-Hao Tao

Ping-Lang Ruan

Jun Zhang

Yong Zhou

Cha-Xiang Guan

Affiliations

Soon will be listed here.

Abstract

Cyclin-dependent kinases (CDKs) are overexpressed in tumor cells, and their aberrant activation can promote the progression of non-small-cell lung cancer (NSCLC). We utilized structure-based virtual screening and experimental validation to screen for potential CDKs antagonists among TargetMol natural products. Molecular docking and molecular dynamics simulation results indicate that Dolastatin 10 exhibits strong interactions with multiple subtypes of CDKs (CDK1, CDK2, CDK3, CDK4, and CDK6), forming stable CDKs-Dolastatin 10 complex compounds. Furthermore, in vitro experiments demonstrate that Dolastatin 10 significantly inhibits the viability, migration, and invasion of H1299 cells in a concentration-dependent manner, arresting the cell cycle at the G2/M phase by inducing cell senescence. These findings suggest that Dolastatin 10 may serve as a potential CDKs antagonist deserving further investigation.

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