TGR5 receptor agonist, potent and selective
CAS：1199796-29-6
分子式：C27H46O5
分子量：450.65
纯度：98%
存储：Store at -20°C

Background:

INT-777 (S-EMCA) is a potent and selective agonist of TGR5 receptor with EC50 value of 0.82 μM [1].

TGR5 receptor is a G protein-coupled receptor and functions as a cell surface receptor for bile acids. TGR5 receptor plays an important role in the regulation of energy homeostasis by bile acids and suppression of macrophage functions [1].

INT-777 (S-EMCA) is a potent and selective TGR5 receptor agonist [1]. In macrophages, INT-777 inhibited proinflammatory cytokine production by TGR5-induced cAMP signaling and subsequent NF-kB inhibition [2]. In pancreatic β cell line MIN6, INT-777 selectively activated Gαs and increased intracellular cAMP and Ca2+. INT-777 also increased phosphoinositide (PI) hydrolysis and insulin release, which was dependent on Gs/cAMP/Ca2+ pathway [3]. In human podocytes with high glucose, INT-777 induced mitochondrial biogenesis, increased fatty acid β-oxidation and decreased oxidative stress [4].

In Ldlr- /- Tgr5+/+ mice, INT-777 activated TGR5 and attenuated atherosclerosis, which was associated with less plaque macrophage content and decreased intraplaque inflammation [2]. In diabetic db/db mice, INT-777 decreased mitochondrial H2O2 production and increased SOD2 activity, then reduced proteinuria, mesangial expansion, podocyte injury, fibrosis, and CD68 macrophage infiltration in the kidney [4].

参考文献:
[1].  Pellicciari R, Gioiello A, Macchiarulo A, et al. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem, 2009, 52(24): 7958-7961.
[2].  Pols TW, Nomura M, Harach T, et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab, 2011, 14(6): 747-757.
[3].  Kumar DP, Rajagopal S, Mahavadi S, et al. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic β cells. Biochem Biophys Res Commun, 2012, 427(3): 600-605.
[4].  Wang XX, Edelstein MH, Gafter U, et al. G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes. J Am Soc Nephrol, 2015. pii: ASN.2014121271.