TUG-770 (TUG770) is a novel, highly potent agonist of free fatty acid receptor 1 (FFA1/GPR40) with EC50 of 6 nM for hFFA1. TUG-770 possesses the ability to treat Type 2 Diabetes. GPR40, also known as free fatty acid receptor 1, is a new target for the treatment of type 2 diabetes because it increases the amount of insulin secreted from pancreatic β-cells in response to glucose stimulation.
Physicochemical Properties
| Molecular Formula | C19H14FNO2 |
| Molecular Weight | 307.31836 |
| Exact Mass | 307.1 |
| Elemental Analysis | C, 74.26; H, 4.59; F, 6.18; N, 4.56; O, 10.41 |
| CAS # | 1402601-82-4 |
| PubChem CID | 66553168 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 523.5±50.0 °C at 760 mmHg |
| Flash Point | 270.4±30.1 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.614 |
| LogP | 3.68 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 23 |
| Complexity | 523 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1=C(CCC(O)=O)C=CC(C#CC2=C(CC#N)C=CC=C2)=C1 |
| InChi Key | KIZUBVPJNPVIIN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C19H14FNO2/c20-18-13-14(6-8-17(18)9-10-19(22)23)5-7-15-3-1-2-4-16(15)11-12-21/h1-4,6,8,13H,9-11H2,(H,22,23) |
| Chemical Name | 3-[4-[2-[2-(cyanomethyl)phenyl]ethynyl]-2-fluorophenyl]propanoic acid |
| Synonyms | TUG 770; TUG-770; TUG770 |
| HS Tariff Code | 2934.99.03.00 |
| 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
| Targets | Human GPR40/FFA1 ( EC50 = 6 nM ) |
| ln Vitro |
TUG-770 (Compound 22) displays excellent physicochemical and in vitro ADME properties, with good aqueous solubility, good chemical stability, low lipophilicity, and decreased plasma protein binding (PPB). In the Caco-2 cell assay, TUG-770 demonstrates good permeability and excellent stability toward human liver microsomes (HLM)[1]. TUG-770 demonstrates reduced potency when tested on the rodent orthologs (rFFA1, pEC50 = 6.49; mFFA1, pEC50 = 6.83)[1]. TUG-770 considerably boosts insulin secretion in the rat INS-1E cell line at high glucose concentrations (12.4 mM) (10.75% of total content with 10 μM 22 vs. 8.74 with vehicle) and has no effect at low glucose concentrations (2.8 mM) (4.14% of total content with 10 μM 22 vs. 4.02 with vehicle)[1]. |
| ln Vivo | TUG-770 (Compound 22; 20 mg/kg; oral administration; daily; for 28 days) treatment improves glucose tolerance significantly while having no effect on food intake, body weight, body composition, or plasma leptin concentration. The insulin sensitivity index (plasma glucose x plasma insulin) is likewise markedly enhanced by TUG-770 [1]. |
| Animal Protocol |
C56B1/6 male mice (5-6 weeks of age) fed on the 60% fat diet D12492 20 mg/kg Oral administration; daily; for 28 days |
| References |
[1]. Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2013 May 9;4(5):441-445. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 100 mg/mL (~325.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 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 (8.13 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 | 3.2539 mL | 16.2697 mL | 32.5394 mL | |
| 5 mM | 0.6508 mL | 3.2539 mL | 6.5079 mL | |
| 10 mM | 0.3254 mL | 1.6270 mL | 3.2539 mL |