Discovery of Novel CRK12 Inhibitors for the Treatment of Human African Trypanosomiasis: An Integrated Computational and Experimental Approach.

ABSTRACT: Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale mo

SUBMITTER: Li Q 

PROVIDER: S-EPMC12196357 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature