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Purity: ≥98%
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.
| Targets |
Human GPR40/FFA1 ( EC50 = 6 nM )
TUG-770 targets Free Fatty Acid Receptor 1 (FFA1/GPR40) [1] |
|---|---|
| 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].
1. In normal mice, TUG-770 (administered intraperitoneally) was evaluated in an acute intraperitoneal glucose tolerance test (IPGTT), and its effect on glucose tolerance was compared with vehicle and sitagliptin (10 mg/kg, positive control); the results showed that TUG-770 had an impact on acute glucose tolerance in normal mice (means ± standard errors, n = 6, with statistical significance marked as , p < 0.05; , p < 0.01; , p < 0.001) [1] 2. In diet-induced obese (DIO) mice, TUG-770 was tested in an oral glucose tolerance test (OGTT) in both acute (4 weeks of vehicle pretreatment followed by TUG-770 treatment) and chronic (4 weeks of TUG-770 treatment) settings, with a vehicle control group; TUG-770 efficiently normalized glucose tolerance in DIO mice, and this effect was fully sustained after 29 days of chronic dosing (means ± standard errors, n = 6, with statistical significance marked as , p < 0.05; , p < 0.01; , p < 0.001) [1] 3. In Sprague–Dawley rats treated with TUG-770 via oral administration, the compound altered plasma glucose levels and plasma insulin levels in a statistically significant manner (means ± standard errors, n = 6, with statistical significance marked as , p < 0.05; , p < 0.01; , p < 0.001) [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 1. Acute IPGTT experiment in normal mice: Mice were dosed intraperitoneally (ip) with TUG-770, vehicle, or sitagliptin (10 mg/kg as a positive control); glucose tolerance was assessed after dosing, and experimental data were presented as means ± standard errors with a sample size of n = 6, and statistical significance was determined (marked as , p < 0.05; , p < 0.01; , p < 0.001) [1] 2. Chronic OGTT experiment in DIO mice: The experiment was divided into three groups: an acute group (4 weeks of vehicle pretreatment before TUG-770 treatment), a chronic group (4 weeks of continuous TUG-770 treatment), and a vehicle control group; the chronic dosing of TUG-770 lasted for 29 days, glucose tolerance was evaluated via OGTT, and data were recorded as means ± standard errors (n = 6) with statistical significance indicated by , , [1] 3. Glucose and insulin level assessment in Sprague–Dawley rats: TUG-770 was administered to Sprague–Dawley rats via oral dosing; plasma glucose levels and plasma insulin levels were measured at relevant time points after administration, experimental data were expressed as means ± standard errors (n = 6), and statistical significance was analyzed (marked as , p < 0.05; , p < 0.01; , p < 0.001) [1] |
| ADME/Pharmacokinetics |
Literature reports that TUG-770 has good physicochemical properties and pharmacokinetic characteristics, but specific parameters (such as absorption, distribution, metabolism, excretion, half-life, and oral bioavailability) are not provided [1].
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| References | |
| Additional Infomation |
1. Free fatty acid receptor 1 (FFA1/GPR40) can enhance insulin secretion from pancreatic β cells in response to glucose stimulation, and is a new target for the treatment of type 2 diabetes[1]. 2. TUG-770 is a highly effective FFA1/GPR40 agonist. Studies have shown that it has good physicochemical properties and pharmacokinetic characteristics[1]. 3. TUG-770 is suitable for the treatment of type 2 diabetes because it can effectively improve glucose tolerance in diet-induced obese mice, and this therapeutic effect can be fully maintained after 29 days of continuous administration[1].
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| Molecular Formula |
C19H14FNO2
|
|---|---|
| Molecular Weight |
307.31836
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| Exact Mass |
307.1
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| Elemental Analysis |
C, 74.26; H, 4.59; F, 6.18; N, 4.56; O, 10.41
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| CAS # |
1402601-82-4
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| PubChem CID |
66553168
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
523.5±50.0 °C at 760 mmHg
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| Flash Point |
270.4±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.614
|
| LogP |
3.68
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
23
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| Complexity |
523
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1=C(CCC(O)=O)C=CC(C#CC2=C(CC#N)C=CC=C2)=C1
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| InChi Key |
KIZUBVPJNPVIIN-UHFFFAOYSA-N
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| 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
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| Synonyms |
TUG 770; TUG-770; TUG770
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| HS Tariff Code |
2934.99.03.00
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| 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)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (~325.4 mM)
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|---|---|
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 In vivo evaluation of22(TUG-770) in mice on glucose tolerance.ACS Med Chem Lett. 2013 May 9; 4(5): 441–445. |
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 In vivo evaluation of22 (TUG-770)in Sprague–Dawley rats on glucose tolerance after oral dosing.ACS Med Chem Lett. 2013 May 9; 4(5): 441–445. |
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