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Small Molecule Glucokinase Activators as Glucose Lowering Agents: A New Paradigm for Diabetes Therapy

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Glucokinase (GK) is a molecular sensor that regulates glucose induced insulin secretion in pancreatic β-cells and glucose homeostasis in the liver via catalysis of glucose to glucose-6-phosphate. The recent discovery and development of small molecule glucokinase activators represents a potentially important development for the management of type 2 diabetes. Since the discovery of the first orally active small molecule GK activator RO0281675, a number of research groups have reported the identification of potent activators. In this review, the biological significance of GK in whole body glucose homeostasis is briefly described coupled with the recent progress regarding the identification of novel small molecule GK activators.
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Keywords: Glucokinase activator; RO0281675; nicotinamide; permanent neonatal diabetes mellitus (PNDM); spirocyclopropane

Document Type: Research Article

Affiliations: Department of Discovery Chemistry, Roche Research Center, 340 Kingsland St., Nutley, New Jersey 07110, USA.

Publication date: 2006-06-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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