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• W4310857764 startingPage "114994" @default.
• W4310857764 abstract "Phenotypic screening still plays an important role in discovering new drugs, especially for diseases with complex pathogenesis, such as diabetes. As excessive gluconeogenesis is considered an important factor in the occurrence of hyperglycemia in T2DM, we previously screened our compounds library for active molecules which inhibit gluconeogenesis, resulting in the discovery of SL010110 with a unique mechanism, different from metformin and a thienopyridine derivative (DMT). The SARs study of SL010110 led to the discovery of 10v. Compared with SL010110, 10v showed improved anti-gluconeogenesis potency and pyruvate tolerance. A further pharmacokinetic study demonstrated that 10v displayed a relatively short half-life, moderate volume of distribution, and moderate to high oral bioavailability. In vivo chronic experiments showed an improved capability of 10v in ameliorating hyperglycemia as the 5 mg/kg 10v treatment greatly reduced non-fasting and fasting blood glucose levels, making it a promising candidate for the treatment of T2DM. The progression from in vitro screening to in vivo testing of the derivatized compounds provided a useful phenotypic screening drug discovery strategy based on the inhibition of gluconeogenesis." @default.
• W4310857764 created "2022-12-19" @default.
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• W4310857764 date "2023-01-01" @default.
• W4310857764 modified "2023-09-27" @default.
• W4310857764 title "Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM)" @default.
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• W4310857764 doi "https://doi.org/10.1016/j.ejmech.2022.114994" @default.
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