Novel therapeutics based on inhibiting the interaction of glycogen phosphorylase and G_L-subunit of glycogen-associated protein phosphatase 1: WO2009127723

Abstract

Diabetes mellitus is a major challenge for healthcare systems worldwide because it is strongly associated with several major health risk factors. Currently marketed drugs are insufficient to achieve long-term control of blood glucose levels and induce considerable side effects. The development of more effective drugs for metabolic diseases is still of urgent interest. Recently, inhibiting the interaction of hepatic glycogen-targeting subunit (G_L) of protein phosphatase 1 and glycogen phosphorylase a (GPa) is emerging as a novel mechanism to combat diabetic hyperglycemia by dephosphorylation and activation of glycogen synthase, converting high blood glucose to liver glycogen. Patent WO2009127723 describes a variety of arylsulfonylaminomethylphosphonic acids as small molecule inhibitors of G_L–GPa interaction and their potential use as pharmaceutical compositions to treat type 1 and type 2 diabetes mellitus. Although lacking detailed in vivo biological data, WO2009127723 represents the first evidence for the novel rationale in antidiabetic pursuit, meriting the attention of the antidiabetic community.

Keywords::

• diabetes mellitus
• glycogen metabolism
• glycogen phosphorylase
• glycogen synthase
• hepatic glycogen-targeting subunit
• protein phosphatase 1

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