Glycogen phosphorylase inhibition as a therapeutic target: a review of the recent patent literature

There are three human isoforms of glycogen phosphorylase (GP) distinctly located in brain, liver and skeletal muscle tissue. Pharmacological inhibition of glycogen phosphorylase activity in liver is a proposed strategy to attenuate overproduction of glucose and hence limit the pathogenic consequences of chronic hyperglycaemia in Type 2 diabetes. The fact that many GP inhibitors appear most active only while blood glucose levels are high provides this class of drug with an attractive clinical profile. Proof-of-concept appears robust in preclinical models but final validation in humans is still required. GP inhibitors are most commonly proposed as potential therapies for the treatment of Type 2 diabetes and related diabetic complications, giving cardioprotection and antitumour properties. This review outlines the claims of the recent patent literature relating to novel structures of GP inhibitors and their mechanism of action as a therapeutic agent.