MR-2088

MR-2088 is a selective, small molecule inhibitor of Unc-51 like autophagy activating kinase 1 and 2 (ULK1/2). Developed by researchers at the Moffitt Cancer Center, it is a 7-azaindole-derived compound designed to abrogate the autophagy pathway, which serves as a stress-adaptive survival mechanism in mutant RAS-driven tumors. MR-2088 has demonstrated the ability to inhibit stimuli-induced autophagic flux and enhance the anti-tumor activity of RAF-MEK-ERK pathway inhibitors (such as MEK or ERK inhibitors) in KRAS-mutant models, including non-small cell lung cancer (NSCLC). By disrupting autophagy-supported adaptive programs, MR-2088 aims to overcome drug-tolerant persister (DTP) states and limit resistance to KRAS pathway blockade.