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Biological activity
Description
Target:
In Vivo
VU0119498 (0.1-2 mg/kg; a single i.p.) improves glucose tolerance and insulin secretion in mice in a β-cell M3R-dependent fashion[3]. VU0119498 (0.5 mg/kg; a single i.p.) improves glucose tolerance and insulin secretion in obese, glucose-intolerant mice[3]. Animal Model: Male WT mice (12 weeks)[3] Dosage: 0.1, 0.5, 2 mg/kg Administration: A single i.p. Result: Caused a significant improvement in glucose tolerance at the dose of 0.5 mg/kg. Significantly augmented GSIS at the dose of 0.5 mg/kg.
In Vitro
VU0119498 (0.01-30 μM; 150 s) potentiates Ach responses in M1, M3, and M5-expressing CHO cells, with EC50s of 6.04, 6.38, and 4.08 µM, respectively[1]. VU0119498 (3-20 μM) augments ACh-mediated increasing in insulin secretion and intracellular calcium levels in MIN6-K8 cells[3]. VU0119498 (20 μM; 90 min) enhances ACh-induced insulin release in mouse and human pancreatic islets[3].
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Bridges TM, et, al. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem. 2009 Jun 11;52(11):3445-8.
[2]. Bridges TM, et, al. Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1972-5.
[3]. Zhu L, et, al. Allosteric modulation of β-cell M 3 muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18684-18690.
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