Adomeglivant

Adomeglivant is an allosteric antagonist of the glucagon receptor.^1,2 It inhibits glucagon-induced increases in cAMP levels in HEK293 cells expressing the rat glucagon or GLP-1 receptors (IC₅₀s = 1.8 and 1.2 µM, respectively) but has no effect on cAMP levels when used alone.² Adomeglivant also inhibits increases in cAMP levels induced by GLP-1 or exendin-4 (48-86) amide (Item No. 11096) in HEK293 cells expressing the GLP-1 receptor (IC₅₀s = 7 and 12 µM, respectively). It decreases glucose-stimulated insulin secretion when used at a concentration of 1 µM in combination with the GLP-1 receptor antagonist exendin (9-39) in isolated human islets but not glucose-stimulated glucagon secretion when used alone or in combination with exendin (9-39) in isolated mouse islets.³

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1. Li, Y., Ye, Z., Bellman, T.M., et al. Efficient synthesis of β-CF3/SCF3-substituted carbonyls via copper-catalyzed electrophilic ring-opening cross-coupling of cyclopropanols. Org. Lett. 17(9), 2186-2189 (2015).

2. Chepurny, O.G., Matsoukas, M.-T., Liapakis, G., et al. Non-conventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput FRET assays for cAMP. The Journal of Biological Chemisty 294, 3514-3531 (2019).

3. Zhu, L., Dattaroy, D., Pham, J., et al. Intraislet glucagon signaling is critical for maintaining glucose homeostasis. JCI Insight 4(10), e127994 (2019).