| Identification | Back Directory | [Name]
MZ-101/GYS1-IN-2 | [CAS]
2839908-40-4 | [Synonyms]
MZ-101/GYS1-IN-2
2-Pyrrolidinecarboxamide, 4-fluoro-N-[(S)-[4-(1-methylethyl)phenyl]phenylmethyl]-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]-, (2S,4R)- | [Molecular Formula]
C25H28FN5O2 | [MOL File]
2839908-40-4.mol | [Molecular Weight]
449.52 |
| Chemical Properties | Back Directory | [Boiling point ]
738.824±60.00 °C(Press: 760.00 Torr)(predicted) | [density ]
1.285±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
8.987±0.10(predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
MZ-101 (GYS1-IN-2) is an orally active, potent and selective small-molecule glycogen synthase 1 (GYS1) inhibitor with with an IC50 value of 0.041 μM. MZ-101 reduces glycogen concentrations in cells and in mice. MZ-101 can used to study GYS1 -mediated Pompe disease and other glycogen storage diseases[1][2][3]. | [in vivo]
MZ-101 (2-200 mg/kg, p.o., a single dose for 5 h) inhibits GYS1 but not GYS2 de novo glycogen synthesis and reduces glycogen combined with substrate reduction therapy in WT and Pompe mice[2].
| Animal Model: | Male C57Bl6 mice between 7 and 10 weeks old and male Pompe mice between 10 and 32 weeks old[2] | | Dosage: | 2-200 mg/kg | | Administration: | p.o., a single dose for 5 h | | Result: | Reduced incorporation of glucose into glycogen in skeletal and cardiac muscles of both WT and GAA KO mice in a dose-dependent manner. |
| [References]
[1] David John Morgans, et al. Inhibitors of glycogen synthase 1 (gys1) and methods of use thereof. WO2022198196. 2022-09-22.
[2] Ullman JC, et al. Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders. Sci Transl Med. 2024 Jan 17;16(730):eadf1691. DOI:10.1126/scitranslmed.adf1691
[3] Gaspar RC, et al. Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease. Am J Physiol Endocrinol Metab. 2024 Oct 1;327(4):E524-E532. DOI:10.1152/ajpendo.00175.2024 |
|
|