Mini Reviews in Medicinal Chemistry - Volume 10, Issue 12, 2010

Special issue of Mini-Reviews in Medicinal Chemistry dedicated to the memory of Nikos G. Oikonomakos (1945-2008). Glycogenolysis is the phosphorolytic degradation of the storage polysaccharide glycogen to glucose-1-phosphate which, after subsequent transformations to glucose-6-phosphate and glucose, may serve as an energy source for the organism's cells. The rate determining phosphorylation step of the proce Read More

The quest for the discovery of new antihyperglycaemic agents has been more intense the last years due to the rapid increase of mortality associated with type 2 diabetes. Glycogen metabolism has been one of the major causes of the elevated blood glucose levels; hence, special attention has been drawn to the control of the enzymes implicated in the relevant pathway. To this end, the allosteric enzyme of glycoge Read More

Among the variety of approaches for pharmacological intervention in T2DM, the inhibition of GP with the aim of reducing hepatic glucose output is a validated and thoroughly investigated strategy. Both the academia and health companies participate in the search of potent inhibitors, that might be suitable for long-term treatment. As several inhibitory sites have been identified for GP, interest focuses mainly on structures that ca Read More

Glycogen phosphorylase (GP) is a promising molecular target for the treatment of Type 2 diabetes. The design of potential inhibitors for the catalytic site of the enzyme is based on the high affinity for β-D-glucopyranose and the presence of a β-cavity that extends from the sugar anomeric position forming a 15 x 7.5 x 10 A available space. This review is focused on our efforts towards the design and synthesis of va Read More

Glycogen Phosphorylase (GP) is an important target for the development of anti-hyperglycaemic drugs. GP is an enzyme which is moderated allosterically with multiple ligand binding sites where inhibitors can potentially modulate enzyme activity. The search for potent and isoform selective inhibitors of GP is ongoing with an increasing focus on allosteric inhibition. In this review, the structural diversity, and enzyme in Read More

Glycogen phosphorylase is an important therapeutic target for the potential treatment of type 2 diabetes. The importance of computation in the search for potent, selective and drug-like glycogen phosphorylase inhibitors which may eventually lead to antihyperglycemic drugs is now firmly established. Acting solo or more effectively in combination with experiment in a multidisciplinary approach to structure based drug desig Read More

Liver glycogen is synthesized in the postprandial state in response to elevated concentrations of glucose and insulin or by activation of neuroendocrine signals and it is degraded in the postabsorptive state in response to changes in the concentrations of insulin and counter-regulatory hormones. Dysregulation of either glycogen degradation or synthesis through changes in allosteric control or covalent modification of gl Read More

Brain ischemia resulting from multiple disease states including cardiac arrest, stroke and traumatic brain injury, is a leading cause of death and disability. Despite significant resources dedicated to developing pharmacological interventions, few effective therapeutic options are currently available. The basic consequence of cerebral ischemia, characterized by energy failure and subsequent brain metabolic abnormalities, Read More