428815-75-2Relevant academic research and scientific papers
New β-alanine derivatives are orally available glucagon receptor antagonists
Lau, Jesper,Behrens, Garsten,Sidelmann, Ulla G.,Knudsen, Lotte B.,Lundt, Behrend,Sams, Christian,Ynddal, Lars,Brand, Christian L.,Pridal, Lone,Ling, Anthony,Kiel, Dan,Plewe, Michael,Shi, Shengua,Madsen, Peter
, p. 113 - 128 (2007/10/03)
A weak human glucagon receptor antagonist with an IC50 of 7 μM was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.
Glucagon antagonists/inverse agonists
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, (2008/06/13)
Novel compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorde
