MAN1A1 inhibitor

MAN1A1 inhibitors are a class of therapeutic agents that target Mannosidase Alpha Class 1A Member 1 (MAN1A1), an enzyme involved in the maturation of N-glycans in the Golgi apparatus. In non-small cell lung cancer (NSCLC), MAN1A1 has been identified as a key mediator of resistance to immune checkpoint inhibitors (ICIs). High expression of MAN1A1, particularly in vascular endothelial cells (VECs), leads to the reprogramming of the tumor microenvironment into an immunosuppressive state. This state is characterized by the recruitment of pro-tumor neutrophils and the impairment of T- and B-cell immunity through signaling pathways such as ANXA1-FPR1 and NAMPT-integrin. By inhibiting MAN1A1, these agents aim to reverse this vascular-endothelial reprogramming, promote T-cell recruitment via LGALS9-CD45 signaling, and restore the efficacy of ICI therapies. Research presented at ASCO 2026 highlights MAN1A1 as both a predictive biomarker for ICI response and a promising therapeutic target for overcoming resistance in NSCLC.

Other names

MAN1A1 inhibitorsMAN-1A1 inhibitorsMAN 1A1 inhibitorsalpha-1,2-mannosidase IA inhibitor