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Glycogen synthase kinase 3 inhibitors: Proof of concept and therapeutic opportunities for the treatment of diabetes, Alzheimer's disease, stroke and bipolar disorder

  • ID: 10736
  • November 2002
  • Lead Discovery
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Since the mid-1990s there has been a near exponential rise in the level of glycogen synthase kinase-3 (Gsk-3) related research. Consequently the therapeutic potential of Gsk-3 inhibitors has become a major area of pharmaceutical interest. This report offers a state of the art overview of Gsk-3 and analyses the therapeutic role that inhibitors of this enzyme may play. The report concludes that there is particularly strong evidence to support the development of Gsk-3 inhibitors as: 1) antihyperglycemic, insulin sensitizing and insulinotropin agents for use in diabetics 2) inhibitors of neuronal apoptosis and neurological decline in stroke patients 3) blockers of the accumulation and toxicity of Aß/tau in Alzheimer's disease. In addition, the Gsk-3 inhibitory activity of diverse mood stabilizers suggests that bipolar disorder represents a further indication for this therapeutic class. Having demonstrated significant proof of concept to support the development of Gsk-3 inhibitors for each of these conditions we introduce each disease describing clinical characteristics, epidemiology and current treatment practices. We conclude that each condition is a common, serious and unmet disease.Furthermore READ MORE >

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SummaryBackgroundGSK-3 biochemistryGSK-3 substrates Mechanism of substrate phosphorylation by GSK-3 Control of enzyme activity by serine phosphorylation Regulation of enzyme activity by tyrosine phosphorylation Regulation of enzyme activity through a dependence on multiple interacting pathways Therapeutic indications for GSK-3 inhibitorsDiabetes/insulin resistance Epidemiology Clinical overview Current treatment strategies Proof of concept for pathophysiological involvement of GSK-3/therapeutic effect of GSK-3 inhibition Alzheimer's disease Epidemiology Clinical overview Current treatment strategies Proof of concept for pathophysiological involvement of GSK-3/therapeutic effect of GSK-3 inhibition Bipolar disease Epidemiology Clinical overview Current treatment strategies Proof of concept for pathophysiological involvement of GSK-3/therapeutic effect of GSK-3 inhibition Diseases associated with apoptosis An overview of apoptosis Myocardial infarction Epidemiology Clinical overview Current treatment strategies Stroke Epidemiology Clinical overview Current treatment strategies Involvement of apoptosis in stroke and myocardial infarction Involvement of GSK-3 in neuronal and myocardial apoptosis/therapeutic effect of GSK-3 inhibition in stroke and myocardial infarction Disease incidence and market valuesDiabetes/insulin resistance Alzheimer's disease Bipolar disease Stroke/apoptosis inhibitors Current development activityGSK-3 inhibitors Diabetes/insulin resistance Drugs in development or on the market classified by pharmacology, phase and company Profiles of marketed products or molecules in advanced development Trend analysis Co-developers & In-licensers Alzheimer's disease Drugs in development or on the market classified by pharmacology, phase and company Profiles of marketed products or molecules in advanced development Trend analysis Co-developers & In-licensers Bipolar disease Drugs in development or on the market classified by pharmacology, phase and company Profiles of marketed products or molecules in advanced development Co-developers & In-licensers Apoptosis antagonists Drugs in development or on the market classified by pharmacology, phase and company Profiles of marketed products or molecules in advanced development Trend analysis Co-developers & In-licensers Strategic analysisAbout the contributors to this reportDr Jon Goldhill: Dr Jon Goldhill has over 10 years of academic and industrial research experience including 5 years in middle management at the French pharmaceutical giants, Sanofi-Synthelabo. Focussing on a variety of indications including inflammatory disorders, GI disease, Urological conditions and cancer, Dr Goldhill was responsible for target identification and project development. Dr Goldhill is now CEO and chief analyst at LeadDiscovery and coordinates the identification of candidate drug discovery projects with industrial potential.

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