INT-767 sodium, the sodium salt of INT767, is a novel and potent TGR5 (G-protein coupled)/Farnesoid X-activated receptor agonist with the potential to be used for the treatment of hepatic fibrosis. As a dual farnesoid X receptor/TGR5 agonist, it has EC50s of 30 and 630 nM, respectively.
Physicochemical Properties
| Molecular Formula | C25H43NAO6S |
| Molecular Weight | 494.660098314285 |
| Exact Mass | 494.267 |
| CAS # | 1000403-03-1 |
| Related CAS # | 1000403-03-1 (sodium);1000403-00-8 (free); |
| PubChem CID | 23712772 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 33 |
| Complexity | 786 |
| Defined Atom Stereocenter Count | 11 |
| SMILES | CC[C@@H]1[C@@H]2C[C@@H](CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3[C@@H]1O)CC[C@@H]4[C@H](C)CCOS(=O)(=O)[O-])C)C)O.[Na+] |
| InChi Key | TXIWHUPIUUZFFK-PMWRKVJASA-M |
| InChi Code | 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 |
| Chemical 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 |
| Synonyms | INT 767 INT767INT-767 INT-767 Free |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | INT-767 is very stable to phase I and phase II enzymatic changes, does not inhibit cytochrome P450 enzymes, does not show cytotoxic effects in HepG2 cells, and does not block potassium channels associated to the human ether-a-go-go gene [2]. |
| ln Vivo | In db/m and db/db mice, INT-767 (10–20 mg/kg; i.p.; once daily for two weeks) lowers plasma total cholesterol and triglyceride levels [2]. |
| Animal Protocol |
Animal/Disease Models: Male 8weeks old C57BKS/J db/db mice, control non-diabetic db/m mice [2] Doses: 10, 20 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 2 weeks Experimental Results: Plasma total cholesterol and triglyceride levels were diminished. |
| References |
[1]. 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]. 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. |
| Additional Infomation | See also: Int-767 (annotation moved to). |
Solubility Data
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~202.16 mM) H2O : ~100 mg/mL (~202.16 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 50 mg/mL (101.08 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0216 mL | 10.1080 mL | 20.2159 mL | |
| 5 mM | 0.4043 mL | 2.0216 mL | 4.0432 mL | |
| 10 mM | 0.2022 mL | 1.0108 mL | 2.0216 mL |