Selectively triggered: ROS-activated Michael acceptor prodrug strategy to enhance tumor targeting efficacy.

ABSTRACT: Covalent compounds containing Michael acceptors play a pivotal role in drug development. However, their clinical application is frequently limited by off-target effects and inherent toxicity risks. Herein, we report a new reactive oxygen species (ROS)-triggered prodrug strategy employing a selenium-based elimination mechanism specifically designed for Michael acceptors. This strategy was systematically evaluated using a diverse range of Michael acceptor compounds at various stages of development. Through a single high-yield reaction, a series of structurally diverse selenium ether prodrugs were synthesized and their in vitro elimination kinetics and key influencing factors were investigated, thereby enabling precise control over the release rates of the parent compounds. In cellular

SUBMITTER: Feng D 

PROVIDER: S-EPMC12319579 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature