Advances in glycogen phosphorylase inhibitor design.
The regulation of glycogen metabolism is a major therapeutic strategy for blood glucose control in type 2 diabetes. Because glycogen phosphorylase catalyzes the first step in the phosphorolysis of glycogen, it has become a potential key target for controlling hyperglycemia in this disease. This review focuses on advances in new, mostly synthetic, molecules that inhibit glycogen phosphorylase, and describes progress in our understanding of the mechanism of action of these inhibitors gained through X-ray crystallographic studies.
Oikonomakos
Nikos G
NG
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, 48 Vassileos Constantinou Avenue, Athens 11635, Greece. ngo@eie.gr
Somsák
László
L
D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D006003:Glycogen; D024981:Glycogen Phosphorylase