Targeting RNA:protein interactions with an integrative approach leads to the identification of potent YBX1 inhibitors.

ABSTRACT: RNA-protein interactions (RPIs) are promising targets for developing new molecules of therapeutic interest. Nevertheless, challenges arise from the lack of methods and feedback between computational and experimental techniques during the drug discovery process. Here, we tackle these challenges by developing a drug screening approach that integrates chemical, structural and cellular data from both advanced computational techniques and a method to score RPIs in cells for the development of small RPI inhibitors; and we demonstrate its robustness by targeting Y-box binding protein 1 (YB-1), a messenger RNA-binding protein involved in cancer progression and resistance to chemotherapy. This approach led to the identification of 22 hits validated by molecular dynamics (MD) simulations and nuclear

SUBMITTER: El Hage K 

PROVIDER: S-EPMC9928419 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature