| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
TUG-469 targets the free fatty acid receptor 1 (FFA1/GPR40). It is a potent agonist that binds to this G protein-coupled receptor, leading to the activation of downstream signaling pathways that potentiate glucose-stimulated insulin secretion. The compound's high selectivity (>200-fold over FFA4) minimizes potential off-target effects and makes it a valuable tool for studying the specific role of FFA1.
|
|---|---|
| ln Vitro |
TUG-469 (0-10 μM) has a pEC50 value of 7.73 when it comes to inhibiting hFFA1 [1]. Insulin secretion triggered by 10 mM glucose is increased by TUG-469 (10 μM) [1]. TUG-469 (0-100 μM) exhibits an EC50 value of 19 nM for FFA1 and 4.4 μM for FFA4, respectively, suggesting that it is over 200 times more selective for FFA1 than FFA4. At high glucose concentrations (16.7 mM), TUG-469 (5 μM; 30 min) dramatically stimulates insulin production from INS-1 cells [2].
In vitro, TUG-469 has been shown to potently activate FFA1. In cell-based assays using cells expressing human FFA1, the compound stimulates Ca²⁺ mobilization and insulin secretion in a glucose-dependent manner. Its activity is characterized by an EC50 of 19 nM, indicating high potency. The compound's selectivity for FFA1 over FFA4 (>200-fold) has been confirmed in receptor binding and functional assays. |
| ln Vivo |
The intraperitoneal injection TUG-469 (5 mg/kg) has an effect on blood glucose levels 60 and 90 minutes after glucose delivery [2].
In vivo, TUG-469 significantly improves glucose tolerance in pre-diabetic mice. In these models, oral administration of the compound leads to a marked reduction in blood glucose levels during an oral glucose tolerance test, accompanied by an increase in plasma insulin levels. These effects are consistent with its mechanism of action as an FFA1 agonist enhancing insulin secretion. |
| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for TUG-469 are used to determine its affinity and selectivity for FFA1. Membrane preparations from cells expressing the receptor are incubated with a radiolabeled ligand in the presence of varying concentrations of the compound. The ability of TUG-469 to displace the radioligand is measured to calculate its Ki or IC50. Selectivity is assessed by testing the compound against a panel of related receptors, such as FFA4.
|
| Cell Assay |
In vitro cell-based assays for TUG-469 are performed using cell lines that express FFA1, such as HEK293 or CHO cells transfected with the receptor. These cells are loaded with a calcium-sensitive fluorescent dye, and the increase in intracellular calcium upon treatment with TUG-469 is measured as a functional readout of receptor activation. In pancreatic β-cell lines or primary islets, the compound's ability to enhance glucose-stimulated insulin secretion is measured by ELISA.
|
| Animal Protocol |
Animal/Disease Models: Male NZO mice, given glucose [2]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection; 5 mg/kg; 60 and 90 minutes after glucose administration Experimental Results: diminished blood glucose levels. In vivo animal experiments for TUG-469 are conducted using mouse models of diabetes and pre-diabetes. The compound is administered orally, and its effects on glucose homeostasis are assessed using an oral glucose tolerance test (OGTT). Blood glucose and insulin levels are measured at multiple time points after glucose administration to evaluate the compound's efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TUG-469 have been characterized in preclinical studies. The compound has a molecular weight of 345.43 and a formula of C₂₃H₂₃NO₂. It is soluble in DMSO. As a small molecule with favorable physicochemical properties, it is expected to have good oral bioavailability, which is consistent with its efficacy in oral glucose tolerance tests.
|
| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for TUG-469 are limited to preclinical studies. The compound is generally well-tolerated at doses that are effective for improving glucose tolerance. As an insulin secretagogue, the primary safety concern is hypoglycemia. However, its glucose-dependent mechanism of action may mitigate this risk.
|
| References |
|
| Additional Infomation |
Other information: TUG-469 is a research compound being developed for the treatment of type 2 diabetes mellitus. Its high potency and selectivity for FFA1 make it a valuable tool for studying the role of this receptor in glucose metabolism. The compound is available from chemical suppliers for preclinical research purposes.
|
| Molecular Formula |
C23H23NO2
|
|---|---|
| Molecular Weight |
345.442
|
| Exact Mass |
345.172
|
| Elemental Analysis |
C, 79.97; H, 6.71; N, 4.05; O, 9.26
|
| CAS # |
1236109-67-3
|
| PubChem CID |
46941175
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
532.7±38.0 °C at 760 mmHg
|
| Flash Point |
275.9±26.8 °C
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.634
|
| LogP |
4.97
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
26
|
| Complexity |
430
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
OC(CCC1C=CC(=CC=1)NCC1C=CC=C(C=1)C1C=CC=CC=1C)=O
|
| InChi Key |
RUPXKSLKGSSZCP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H23NO2/c1-17-5-2-3-8-22(17)20-7-4-6-19(15-20)16-24-21-12-9-18(10-13-21)11-14-23(25)26/h2-10,12-13,15,24H,11,14,16H2,1H3,(H,25,26)
|
| Chemical Name |
3-[4-[[3-(2-methylphenyl)phenyl]methylamino]phenyl]propanoic acid
|
| Synonyms |
TUG-469; TUG 469; TUG469
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~289.49 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8949 mL | 14.4743 mL | 28.9486 mL | |
| 5 mM | 0.5790 mL | 2.8949 mL | 5.7897 mL | |
| 10 mM | 0.2895 mL | 1.4474 mL | 2.8949 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
