Covalent inhibitors possessing autophagy-modulating capabilities: charting novel avenues in drug design and discovery

Abstract

Autophagy is a crucial cellular process in degrading damaged organelles and maintaining cellular homeostasis. By forming irreversible bonds with specific proteins, covalent inhibitors present a distinct advantage in regulating autophagy and its related pathways. These inhibitors can provide sustained modulation of autophagy at lower doses, improving therapeutic efficacy while minimizing adverse effects. We discuss their mechanisms, including how they affect autophagy-related enzymes and pathways, and their potential applications in the treatment of cancers and other autophagy-related disorders. Studying autophagy-related pathway targets will provide new insights for the development of covalent inhibitors and enhance therapeutic strategies for complex conditions.