AR 231453

• CAT Number: I004729
• CAS Number: 733750-99-7
• Molecular Formula: C21H24FN7O5S
• Molecular Weight: 505.52
• Purity: ≥95%
• Target: GPR119
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• InChI: InChI=1S/C21H24FN7O5S/c1-12(2)18-26-21(34-27-18)13-6-8-28(9-7-13)20-17(29(30)31)19(23-11-24-20)25-16-5-4-14(10-15(16)22)35(3,32)33/h4-5,10-13H,6-9H2,1-3H3,(H,23,24,25)
• InChIKey: DGBKNTVAKIFYNU-UHFFFAOYSA-N
• SMILES: O=[N+](C1=C(N2CCC(C3=NC(C(C)C)=NO3)CC2)N=CN=C1NC4=CC=C(S(=O)(C)=O)C=C4F)[O-]

AR231453 is a potent and selective small molecule agonist of GPR119 that enhances glucose-dependent insulin secretion and glucagon-like peptide 1 (GLP-1) release; Antidiabetic agent.IC50 value:Target: GPR119in vitro: The GPR119-specific agonist AR231453 significantly increased cAMP accumulation and insulin release in both HIT-T15 cells and rodent islets. In both cases, loss of GPR119 rendered AR231453 inactive [1]. In GLUTag cells, a well-established model of intestinal L-cell function, the potent GPR119 agonist AR231453 stimulated cAMP accumulation and GLP-1 release [2].in vivo: AR231453 also enhanced glucose-dependent insulin release in vivo and improved oral glucose tolerance in wild-type mice but not in GPR119-deficient mice. Diabetic KK/A(y) mice were also highly responsive to AR231453. Orally active GPR119 agonists may offer significant promise as novel antihyperglycemic agents acting in a glucose-dependent fashion [1]. When administered in mice, AR231453 increased active GLP-1 levels within 2 min after oral glucose delivery and substantially enhanced total glucose-dependent insulinotropic peptide levels. Blockade of GLP-1 receptor signaling with exendin(9-39) reduced the ability of AR231453 to improve glucose tolerance in mice [2].

Reference

[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.
[2]. Chu ZL, et al. A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like Peptide-1 and glucose-dependent insulinotropic Peptide release. Endocrinology. 2008 May;149(5):2038-47.
[3]. Semple G, et al. 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.