2. Academic Validation
  3. Synthesis, in vitro ADME profiling and in vivo pharmacological evaluation of novel glycogen phosphorylase inhibitors

Synthesis, in vitro ADME profiling and in vivo pharmacological evaluation of novel glycogen phosphorylase inhibitors

  • Bioorg Med Chem Lett. 2020 Jul 15;30(14):127117. doi: 10.1016/j.bmcl.2020.127117.
Guang-Xin Miao 1,  You-de Wang 1,  Zhi-Wei Yan 1,  Li-Ying Zhang 2
Affiliations

Affiliations

  • 1 Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, China.
  • 2 Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, China. Electronic address: zzzhangliying@126.com.
PMID: 32527535 DOI: 10.1016/j.bmcl.2020.127117
Abstract

A small set of indole-2-carboxamide derivatives identified from a high-throughput screening campaign has been described as a novel, potent, and glucose-sensitive inhibitors of glycogen phosphorylase a (GPa). Among this series of compounds, compound 2 exhibited moderate GP inhibitory activity (IC50 = 0.29 μM), good cellular efficacy (IC50 = 3.24 μM for HepG2 cells and IC50 = 7.15 μM for isolated rat hepatocytes), together with good absorption, distribution, metabolism, and elimination (ADME) profiles. The in vivo animal study revealed that compound 2 significantly inhibited an increase of fasting blood glucose level in adrenaline-induced diabetic mice.

Keywords

ADME; Biological activity; Blood glucose; Diabetes; Glycogen phosphorylase inhibitors.

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