AR 231453

Uses

AR 231453 is a potent, specific and orally available GPR119 agonist. AR 231453 can stimulate β-cell replication and improve islet graft function s[1][2].

Biological Activity

AR231453 is a 5-nitropyrimidine derivative th at acts as a highly potent and selective GPR119 agonist (EC50/GPR119 species = 0.4 nM/monkey, 1.6 nM/dog, 4.7 nM/hamster, 3.5 nM/human, 12 nM/mouse, 4 nM/r at in cell-based assays), exhibiting no off-target activity toward 216 receptors, enzymes, and orphan GPCRs. AR231453 improves glucose tolerance in mice (3 mg/kg i.p. or 20 mg/kg, p.o.) and rats (3 mg/kg i.p.), while no in vivo efficacy is observed among GPR119-deficient mice.

in vivo

References

[1] Chu ZL, et al. A role for beta-cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucose-dependent insulin release. Endocrinology. 2007 Jun;148(6):2601-9. DOI:10.1210/en.2006-1608
[2] J Gao, et al. Stimulating β-cell replication and improving islet graft function by AR231453, A GPR119 agonist. Transplant Proc. 2011 Nov;43(9):3217-20. DOI:10.1016/j.transproceed.2011.10.021