MZ-101 is a potent, selective inhibitor of glycogen synthase 1 (GYS1) with IC50 of 41 nM (human GYS1), with no inhibition against GYS2.
MZ-101 shows similar potency and selectivity of MZ-101 for the mouse isoform of GYS1.
MZ-101 potently and selectively inhibits GYS1 by a noncompetitive mechanism.
MZ-101 reduces glycogen abundance in a dose-dependent manner in fibroblasts from healthy controls and patients with Pompe disease with a mean EC50 of 500 nM.
MZ-101 inhibits glycogen synthesis across species and cell types expressing GYS1, independent of defects in glycogen catabolism.
MZ-101 inhibits GYS1 but not GYS2 de novo glycogen synthesis in WT and Pompe mice.
