Consensus Pharmacological Interactions for PLK2 Inhibitor Identification in Colorectal Cancer Treatment.

ABSTRACT: PLK2 plays a critical role in cellular stress response, redox regulation, and tumor progression. In colorectal cancer (CRC), elevated PLK2 expression is associated with chemoresistance and poor patient prognosis, making it a compelling target for therapeutic intervention. In this study, we used a structure-based drug discovery strategy to develop a consensus model incorporating pharmacological interactions from various PLK2 structures. This model enhanced the hit rate for identifying inhibitors during virtual screening, increasing the ROC-AUC from 0.906 to 0.930. We then used the model to screen the ChemDiv compound library and identified two novel PLK2 inhibitors. Next, we searched for analogs of the most potent compound and evaluated their activity. Two analogs demonstrated submicromolar

SUBMITTER: Wu YW 

PROVIDER: S-EPMC12801292 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature