INT-767

• CAT Number: I000064
• CAS Number: 1000403-03-1
• Molecular Formula: C25H43NaO6S
• Molecular Weight: 494.66
• Purity: ≥95%
• Target: FXR/TGR5
• Solubility: DMSO: ≥ 205.5 mg/mL
• Storage: Store at -20°C
• IC50: 30 nM(EC50, FXR), 630 nM(EC50, TGR5) [2]
• IUPAC Name: sodium;[(3R)-3-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl] sulfate
• 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
• InChIKey: TXIWHUPIUUZFFK-PMWRKVJASA-M
• SMILES: O[C@@H]1CC[C@@]2(C)[C@@]([C@@H](CC)[C@@H](O)[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC[C@@]4([C@H](C)CCOS(=O)([O-])=O)[H])([H])C1.[Na+]

INT-767 (CAT: I000064) is a synthetic compound that acts as a selective agonist of the farnesoid X receptor (FXR). FXR is a nuclear receptor involved in the regulation of bile acid homeostasis, lipid metabolism, and inflammatory responses. By activating FXR, INT-767 modulates various metabolic pathways, including the regulation of bile acid synthesis, transport, and metabolism. INT-767 has shown potential in the treatment of liver diseases, including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). It represents a novel therapeutic approach targeting FXR to modulate bile acid metabolism and improve liver function in these conditions.

Overview of Clinical Research

INT-767 is  a Farnesoid X-activated receptor agonist and a G protein-coupled receptor agonist. A phase 2 trail of INT-767 in nonalcoholic steatohepatitis(NASH) patients with fibrosis was initiated in 2017. 

 

Reference

1: Rizzo G, Passeri D, De Franco F, Ciaccioli G, Donadio L, Rizzo G, Orlandi S, Sadeghpour B, Wang XX, Jiang T, Levi M, Pruzanski M, Adorini L. Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. Mol Pharmacol. 2010 Oct;78(4):617-30. doi: 10.1124/mol.110.064501. Epub 2010 Jul 14. PubMed PMID: 20631053; PubMed Central PMCID: PMC2981390.
2: Baghdasaryan A, Claudel T, Gumhold J, Silbert D, Adorini L, Roda A, Vecchiotti S, Gonzalez FJ, Schoonjans K, Strazzabosco M, Fickert P, Trauner M. Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO⁻₃ output. Hepatology. 2011 Oct;54(4):1303-12. doi: 10.1002/hep.24537. PubMed PMID: 22006858; PubMed Central PMCID: PMC3744065.
3: Wang XX, Luo Y, Wang D, Adorini L, Pruzanski M, Dobrinskikh E, Levi M. A Dual Agonist of Farnesoid X Receptor (FXR) and the G protein-coupled Receptor TGR5, INT-767, Slows Down Age-Related Kidney Disease in Mice. J Biol Chem. 2017 Jun 8. pii: jbc.C117.794982. doi: 10.1074/jbc.C117.794982. [Epub ahead of print] PubMed PMID: 28596381.