NRX-8766

NRX-8766 is a small molecule intramolecular glue inhibitor of CBL-B (Casitas B-lineage lymphoma proto-oncogene B), an E3 ubiquitin ligase that serves as a master regulator of peripheral T-cell activation. Developed by Nurix Therapeutics, NRX-8766 functions by stabilizing the autoinhibited, closed conformation of CBL-B, effectively preventing its ligase activity. In preclinical studies, NRX-8766 has demonstrated the ability to significantly increase T-cell activation markers and the secretion of pro-inflammatory cytokines such as IL-2, IFN-gamma, and TNF-alpha. Oral administration of the compound in syngeneic tumor models has shown potent anti-tumor efficacy, mimicking the phenotype of CBL-B genetic knockout and positioning it as a promising candidate for cancer immunotherapy.