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L-168,049

Names

[ CAS No. ]:
191034-25-0

[ Name ]:
L-168,049

[Synonym ]:
Glucagon Receptor Antagonist II
Nalmefene-d3
L-168,049

Biological Activity

[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].

[Related Catalog]:

Research Areas >> Metabolic Disease
Signaling Pathways >> GPCR/G Protein >> Glucagon Receptor

[Target]

IC50: 3.7 nM (human glucagon receptor), 63 nM (murine glucagon receptor), and 60 nM (canine glucagon receptor)[2]


[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].

[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].

[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.

Chemical & Physical Properties

[ Density]:
1.367g/cm3

[ Boiling Point ]:
542.3ºC at 760mmHg

[ Molecular Formula ]:
C24H20BrClN2O

[ Molecular Weight ]:
467.78500

[ Flash Point ]:
281.8ºC

[ Exact Mass ]:
466.04500

[ PSA ]:
37.91000

[ LogP ]:
7.61540

[ Vapour Pressure ]:
2.83E-11mmHg at 25°C

[ Index of Refraction ]:
1.626

Related Compounds