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Overview
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Background
AR 231453 is an agonist of GPR119 with EC50 value of 0.68nM [1].
AR 231453 is the first subnanomolar agonist of GPR119. It is highly selective against GPR119 over a 76 receptor and enzyme profiling panel (CEREP) including the known incretin receptors. It also has no activity to 140 known and orphan GPCRs in melanophore dispersion assays. Besides that, AR 231453 is reported to stimulate cAMP production via endogenously expressed GPR119 in HIT-T15 cell line with EC50 value of 4.7nM [1].
In vivo assay shows that AR 231453 has activity in rodents. It can enhance glucose-dependent insulin release and improve oral glucose tolerance in wild-type C57/bl6J mice but not in GPR119-deficient mice at a dose of 20 mg/kg. Due to its activity to active GPR119, AR 231453 is expected to be a potent anti-diabetic agent [1].[1] Semple G, Fioravanti B, Pereira G, Calderon I, Uy J, Choi K, Xiong Y, Ren A, Morgan M, Dave V, Thomsen W, Unett DJ, Xing C, Bossie S, Carroll C, Chu ZL, Grottick AJ, Hauser EK, Leonard J, Jones RM. Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119. J Med Chem. 2008 Sep 11;51(17):5172-5.
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