AN-465

AN-465 is a small-molecule inhibitor of G-protein-signaling modulator 1 (GPSM1) currently in preclinical development for the treatment of atherosclerosis, particularly as a macrovascular complication of diabetes. GPSM1 is a regulator of macrophage chemotaxis and migration; its inhibition by AN-465 suppresses the P38/ERK MAPK signaling pathway via the cAMP/PKA/KLF4/PMP22 axis. In animal models, administration of AN-465 has been shown to reduce atherosclerotic plaque formation and aortic inflammation by decreasing macrophage infiltration into vessel walls. This research was notably presented at the American Diabetes Association (ADA) 2024 meeting by researchers from Shanghai, China.