| Description |
L-168049 is a potent, selective, orally active and non-competitive glucagon receptor antagonist with IC50s of 3.7 nM, 63 nM, and 60 nM for human, murine, and canine glucagon receptors, respectively[1][2].
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| Related Catalog |
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| Target |
IC50: 3.7 nM (human glucagon receptor), 63 nM (murine glucagon receptor), and 60 nM (canine glucagon receptor)[2]
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| In Vitro |
L-168049 (compound 49) inhibits glucagon (100 pM) stimulated cAMP synthesis in CHO cells expressing the human glucagon receptor (hGIAR) (IC50 of 41 nM). L-168049 blocks cAMP formation stimulated by glucagon in murine liver membranes[1]. L-168049 increases the apparent EC50 for glucagon stimulation of adenylyl cyclase in Chinese hamster ovary cells expressing the human glucagon receptor and decreases the maximal glucagon stimulation observed, with a Kb of 25 nM[2].
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| In Vivo |
In the liver of L-G6pc−/- mice, Pck1 mRNA expression is decreased by half 6 h after the administration of L-168049 (50 mg/kg body; p.o.), demonstrating the efficiency of the suppression of glucagon signaling. In agreement with the role of glucagon in the induction of extrahepatic gluconeogenesis, the administration of the L-168049 prevents the increase of the G6pc expression in both the kidneys and intestine of 6 h-fasted L-G6pc−/- mice[3].
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| References |
[1]. S E de Laszlo, et al. Potent, orally absorbed glucagon receptor antagonists. Bioorg Med Chem Lett. 1999 Mar 8;9(5):641-6. [2]. M A Cascieri, et al. Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor. J Biol Chem. 1999 Mar 26;274(13):8694-7. [3]. Elodie Mutel, et al. Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: induction of renal and intestinal gluconeogenesis by glucagon. Diabetes. 2011 Dec;60(12):3121-31.
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