MRT68921

MRT68921 is a potent, small-molecule inhibitor of the Unc-51-like autophagy activating kinases 1 and 2 (ULK1 and ULK2), which are central regulators of the initiation phase of autophagy. By blocking the kinase activity of ULK1/2, MRT68921 prevents the formation of the phagophore, thereby inhibiting autophagic flux. In addition to its role in autophagy, MRT68921 has been shown to inhibit NUAK1 (AMPK-related protein kinase 5), a kinase involved in antioxidant defense and tumor survival. It is widely utilized in preclinical research to investigate the role of autophagy in various pathologies, including oncology (e.g., triple-negative breast cancer, ovarian cancer, and glioblastoma), infectious diseases (e.g., Zika virus and Pseudomonas aeruginosa), and pregnancy-related disorders like preeclampsia. In cancer models, it is often explored as a sensitizing agent to chemotherapy or other targeted therapies by blocking protective autophagy.