GL-320

GL-320 is a potent and selective small-molecule inhibitor of the deubiquitinating enzyme USP10. Developed by researchers at Wayne State University, it is being investigated for its potential to overcome resistance to platinum-based chemotherapy and enhance the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). By inhibiting USP10, GL-320 destabilizes multiple DNA damage response (DDR) and pro-survival proteins, leading to impaired DNA repair, cell cycle arrest, and the induction of autophagy and caspase-dependent apoptosis. Furthermore, GL-320 triggers immunogenic cell death (ICD), characterized by endoplasmic reticulum stress and the exposure of calreticulin, which may stimulate anti-tumor immunity.