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- W1976278317 abstract "Small molecule glucokinase activators (GKAs) continue to represent a potential strategy to treat type 2 diabetes (T2D). Glucokinase (GK) primarily exerts its effect through modulatory actions in pancreatic β-cells and hepatocytes. It couples insulin secretion in the pancreas with plasma glucose concentration and improves glucose utilization in the liver, thus, affecting two key aspects of glucose homeostasis. There has been an intense interest in GKAs within the pharmaceutical industry ever since the first report of a low molecular mass activator in 2003. The key drivers for this interest are the robust glucose lowering activity observed with GKAs in preclinical T2D animal models and early reports of efficacy in T2D patients.The objective is to review GKA structures disclosed during the 2008 - 2010 period and classify them based on key structural features. For this purpose, only compound data from patent disclosures were used.The reader would gain a detailed view of structural diversity of the GKA field disclosed during the review period.There continues to be a high level of interest within the pharmaceutical industry in novel GKAs. Several new and highly potent structure types were reported for the first time in the past 3 years. Common features of all of them include a hydrogen bond donor-acceptor pair that makes contact with the backbone CO- and NH- bonds of Arg 63 residue on GK and two hydrophobic groups. During this review period, several GKAs progressed to Phase II clinical testing and the data on their safety and efficacy profiles are eagerly awaited." @default.
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- W1976278317 date "2010-12-15" @default.
- W1976278317 modified "2023-10-16" @default.
- W1976278317 title "Novel glucokinase activators: a patent review (2008 – 2010)" @default.
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- W1976278317 doi "https://doi.org/10.1517/13543776.2011.542413" @default.
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