MZ101

MZ101 is an orally active, potent, and selective small-molecule inhibitor of glycogen synthase 1 (GYS1), currently in preclinical development by Maze Therapeutics. It is designed as a substrate reduction therapy (SRT) for Pompe disease and other glycogen storage disorders. By inhibiting GYS1, the rate-limiting enzyme for glycogen synthesis in muscle and the nervous system, MZ101 reduces the pathological accumulation of glycogen that leads to autophagolysosomal abnormalities, metabolic dysregulation, and muscle atrophy. Notably, MZ101 is highly selective for the GYS1 isoform (IC50 = 0.041 µM) and shows no inhibition against GYS2, the isoform essential for liver glycogen synthesis, thereby avoiding potential hepatic side effects. Preclinical studies in mouse models of Pompe disease have demonstrated that MZ101 can normalize muscle glycogen levels and correct transcriptional and metabolic abnormalities, both as a monotherapy and in combination with enzyme replacement therapy (ERT).

Other names

GYS1-IN-2GYS-1-IN-2GYS 1-IN-2CAS 2839908-40-4CAS2839908-40-4CAS-2839908-40-4