Abstract #2000

Miller C, Liu H, Duffy J, Parmee E, Zhang B

A 13C and 31P NMR spectroscopic approach was employed in perfused mouse livers metabolizing 13C-labelled substrates to develop a novel ex-vivo assay for the assessment of small molecule glucagon receptor antagonists. Three novel thiophene-derived glucagon receptor antagonists were profiled using this approach. The relative inhibitions of glucagon induced glycogenolysis demonstrated by each compound were consistent with their in vitro activities and were also reliable indicators of their intrinsic activities in the liver. That this information could be gained without the need to optimize dosing and pharmacokinetic parameters demonstrates the value of this technique.