| CAS |
1000403-03-1 |
| English Name |
INT-767 |
| Molecular Formula |
C25H43NaO6S |
| Molecular Weight |
494.66 |
| Solubility |
Soluble in DMSO |
| Purity |
≥98% |
| Appearance |
White to off-white Solid |
| Storage |
Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| SMILES |
C[C@H](CCOS(=O)([O-])=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@H](O)[C@H](CC)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C.[Na+] |
| InChIKey |
TXIWHUPIUUZFFK-PMWRKVJASA-M |
| InChI |
InChI=1S/C25H44O6S.Na/c1-5-17-21-14-16(26)8-11-25(21,4)20-9-12-24(3)18(6-7-19(24)22(20)23(17)27)15(2)10-13-31-32(28,29)30;/h15-23,26-27H,5-14H2,1-4H3,(H,28,29,30);/q;+1/p-1/t15-,16-,17-,18-,19+,20+,21+,22+,23-,24-,25-;/m1./s1 |
| PubChem CID |
23712772 |
| Target Point |
FXR |
| Passage |
Metabolic Enzyme&Protease |
| Background |
INT-767 is a G-protein coupled/Farnesoid X-activated receptor agonist |
| Biological Activity |
INT-767是法尼醇X受体/TGR5双激动剂，平均 EC50 分别为30和630 nM。INT-767 是一种安全有效的 FXR 和 TGR5 依赖性途径的调节剂。[1-2] |
| In Vitro |
INT-767 is a potent agonist for both FXR(mean EC(50)，30 nM by PerkinElmer AlphaScreen assay)and TGR5(mean EC(50)，630 nM by time resolved-fluorescence resonance energy transfer). INT-767 does not show cytotoxic effects in HepG2 cells. INT-767 induces FXR-dependent lipid uptake by adipocytes，with the beneficial effect of shuttling lipids from central hepatic to peripheral fat storage，and promotes TGR5-dependent glucagon-like peptide-1 secretion by enteroendocrine cells，a validated target in the treatment of type 2 diabetes. [2] |
| In Vivo |
Only the dual FXR/TGR5 agonist，INT-767，significantly improved serum liver enzymes，hepatic inflammation，and biliary fibrosis in Mdr2(-/-)mice. In line with this，INT-767 significantly induced bile flow and biliary HCO 3- output，as well as gene expression of carbonic anhydrase 14，an important enzyme able to enhance HCO 3- transport，in an Fxr-dependent manner. In addition，INT-767 dramatically reduced bile acid synthesis via the induction of ileal Fgf15 and hepatic Shp gene expression，thus resulting in significantly reduced biliary bile acid output in Mdr2(-/-)mice.[1] INT-767 treatment markedly decreases cholesterol and triglyceride levels in diabetic db/db mice and in mice rendered diabetic by streptozotocin administration. [2] |
| Data Literature Source |
[1]. Baghdasaryan A，et al. Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mousecholangiopathy model by promoting biliary HCO3- output. Hepatology. 2011 Oct;54(4):1303-1312.
[2]. Rizzo G，et al. Functional characterization of the semisynthetic bile acid derivative INT-767，a dual farnesoid X receptor andTGR5 agonist. Mol Pharmacol. 2010 Oct;78(4):617-630. |
| Unit |
Piece |
| Specification |
5mg |
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