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ID: ALA1139915
Journal: Bioorg Med Chem Lett
Title: PDE-10A inhibitors as insulin secretagogues.
Authors: Cantin LD, Magnuson S, Gunn D, Barucci N, Breuhaus M, Bullock WH, Burke J, Claus TH, Daly M, Decarr L, Gore-Willse A, Hoover-Litty H, Kumarasinghe ES, Li Y, Liang SX, Livingston JN, Lowinger T, Macdougall M, Ogutu HO, Olague A, Ott-Morgan R, Schoenleber RW, Tersteegen A, Wickens P, Zhang Z, Zhu J, Zhu L, Sweet LJ.
Abstract: Modulation of cAMP levels has been linked to insulin secretion in preclinical animal models and in humans. The high expression of PDE-10A in pancreatic islets suggested that inhibition of this enzyme may provide the necessary modulation to elicit increased insulin secretion. Using an HTS approach, we have identified quinoline-based PDE-10A inhibitors as insulin secretagogues in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured.
CiteXplore: 17400452