Glutaminase 1 inhibitors: Therapeutic potential, mechanisms of action, and clinical perspectives.

Glutaminase 1 (GLS1) is a critical enzyme in glutamine metabolism, supporting both energy production and biosynthesis in tumor cells. Inhibitors targeting GLS1 have emerged as promising metabolic therapies. Notably, it exhibits antiproliferative and pro-apoptotic effects in various cancers. This review systematically discusses GLS1's structure and function, the major classes of inhibitors, and the principles behind their design. It also explores the molecular mechanisms underlying GLS1 inhibition, including disruption of glutamine metabolism, induction of oxidative stress, and modulation of key signaling pathways. Furthermore, we evaluated the current clinical applications and therapeutic potential of GLS1 inhibitors in cancer and metabolic disorders. Themes such as drug safety, resistance development, and patient stratification are also addressed. Future research should highlight the potential of combination therapies and precision medicine approaches. Collectively, targeting GLS1 represents a promising strategy with significant translational potential in metabolism-related diseases.