L-168,049
2-(4-Pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)pyrrole

Light beige solid. PROTECT FROM LIGHT. PACKAGED UNDER INERT GAS. A cell-permeable triarylpyrrole compound that acts as a selective, non-competitive, high affinity glucagon receptor antagonist (IC₅₀ = 3.7 nM, 63 nM, and 60 nM for inhibition of labeled glucagon binding to human, murine, and canine glucagon receptor, respectively). Exhibits diminished antagonistic properties in the presence of Mg²⁺ (by ≥ 20-fold) and exhibits poor affinity for the rat, guinea pig, and rabbit glucagon receptors (IC₅₀ > 1 µM). Does not inhibit binding of glucagon-like peptide-1 (GLP-1) to the homologous GLP-1 receptor even at concentrations as high as 10 µM. Does not affect ligand binding of a panel of other GPCRs and only weakly affects p38 kinase activity (IC₅₀ = 1.44 µM). Potently inhibits glucagon-induced GTP_gS binding to G_as (IC₅₀ = 158 nM) and adenylate cyclase activation in hGLUR-CHO cells (K_b = 25 nM). Shown to be orally bioavailable in both mice and rats. Purity: ≥98% by HPLC.

Ref.: Dallas-Yang, Q., et al. 2002. Anal. Biochem. 301, 156. Cascieri, M.A., et al. 1999. J. Biol. Chem. 274, 8694. de Laszlo, S.E., et al. 1999. Bioorg. Med. Chem. Lett. 9, 641.