INT-777 R-enantiomer, a semisynthetic bile acid, is the R-isomer of INT-777 with an EC50 of 4.79 μM for TGR5, and less potent than INT-777 which is a novel and potent TGR5 agonist with an EC50 of 0.82 μM.
Physicochemical Properties
| Molecular Formula | C₂₇H₄₆O₅ |
| Molecular Weight | 450.6511 |
| Exact Mass | 450.334 |
| CAS # | 1198786-98-9 |
| Related CAS # | INT-777;1199796-29-6 |
| PubChem CID | 44605418 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 602.8±55.0 °C at 760 mmHg |
| Flash Point | 332.4±28.0 °C |
| Vapour Pressure | 0.0±3.9 mmHg at 25°C |
| Index of Refraction | 1.539 |
| LogP | 3.99 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 710 |
| Defined Atom Stereocenter Count | 13 |
| SMILES | CC[C@@H]1[C@@H]2C[C@@H](CC[C@@]2([C@H]3C[C@@H]([C@]4([C@H]([C@@H]3[C@@H]1O)CC[C@@H]4[C@H](C)C[C@@H](C)C(=O)O)C)O)C)O |
| InChi Key | NPBCMXATLRCCLF-IRRLEISYSA-N |
| InChi Code | InChi Code InChI=1S/C27H46O5/c1-6-17-20-12-16(28)9-10-26(20,4)21-13-22(29)27(5)18(14(2)11-15(3)25(31)32)7-8-19(27)23(21)24(17)30/h14-24,28-30H,6-13H2,1-5H3,(H,31,32)/t14-,15+,16-,17-,18-,19+,20+,21+,22+,23+,24-,26+,27-/m1/s1 |
| Chemical Name | (2R,4R)-4-[(3R,5S,6R,7R,8R,9S,10S,12S,13R,14S,17R)-6-ethyl-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid |
| Synonyms | INT-777;INT 777;INT777;6-EMCA;S-EMCA |
| 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 |
| 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 Vivo | Compared to CA (4), INT-777 (R enantiomer) is less powerful but more choleretic [1]. |
| References |
[1]. 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 Dec 24;52(24):7958-61. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 100 mg/mL (~221.90 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.55 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 (5.55 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 (5.55 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2190 mL | 11.0951 mL | 22.1902 mL | |
| 5 mM | 0.4438 mL | 2.2190 mL | 4.4380 mL | |
| 10 mM | 0.2219 mL | 1.1095 mL | 2.2190 mL |