| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
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| 50mg |
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| 1g | |||
| Other Sizes |
| Targets |
EC50: 72 nM (GPR40)[1]
Fasiglifam specifically targets GPR40/FFA1, a G protein-coupled receptor that is predominantly expressed in pancreatic β-cells and plays a key role in amplifying glucose-stimulated insulin secretion. It acts as a potent agonist, binding with high affinity (Ki of 38 nM) and exhibiting strong agonistic activity (EC50 of 72 nM). Activation of GPR40 by Fasiglifam enhances glucose-dependent insulin secretion. |
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| ln Vitro |
In vitro, Fasiglifam is a potent and selective GPR40 agonist. In CHO cell lines expressing the human GPR40 receptor, it shows an EC50 of 14 nM and a Ki of 38 nM. It enhances glucose-induced insulin secretion in a glucose-dependent manner in both human and rat islets. This glucose-dependent action is key to its mechanism and a major advantage over other insulin secretagogues.
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| ln Vivo |
In vivo, Fasiglifam has demonstrated efficacy in animal models of type 2 diabetes. In type 2 diabetic rats, it enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia. These effects confirm its potential as an orally active anti-diabetic agent. However, it was noted that Fasiglifam can cause liver damage.
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| Enzyme Assay |
For non-cellular in vitro receptor binding assays, Fasiglifam is characterized using radioligand binding techniques with membranes from cells expressing the human GPR40 receptor. These assays determine its binding affinity (Ki) and confirm its selectivity for GPR40 over other related receptors. Such studies are critical for establishing the compound's mechanism of action as a direct GPR40 agonist.
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| Cell Assay |
For in vitro cellular assays, the activity of Fasiglifam is evaluated in cells expressing GPR40, such as CHO cells. A primary functional assay measures the agonist-induced mobilization of intracellular calcium, as GPR40 is Gq-coupled. The EC50 of 14 nM in CHO cells expressing human GPR40 is determined in such assays. Its effect on glucose-stimulated insulin secretion is also assessed in primary islet cells.
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| Animal Protocol |
For in vivo animal studies, Fasiglifam has been evaluated in rat models of type 2 diabetes. In these studies, the compound is typically administered orally. Its efficacy is assessed by measuring glucose-dependent insulin secretion and improvements in both postprandial and fasting hyperglycemia. These studies demonstrate its in vivo efficacy and support its development as a potential therapeutic agent.
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| ADME/Pharmacokinetics |
Fasiglifam is orally active, indicating favorable oral bioavailability. Its pharmacokinetic profile in animal models has been studied, and it shows properties suitable for once-daily dosing. However, specific parameters such as half-life, clearance, and volume of distribution are not detailed in the provided search results. It is soluble in DMSO for in vitro and in vivo formulation.
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| Toxicity/Toxicokinetics |
Fasiglifam has been associated with liver damage in preclinical and clinical studies. This hepatotoxicity was a significant finding that ultimately impacted its clinical development. Therefore, while it demonstrated efficacy in improving glycemic control, the potential for liver injury is a key safety concern. Comprehensive toxicology studies have been conducted as part of its development program.
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| References |
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| Additional Infomation |
Fasiglifam (TAK-875) is a potent, orally active, and selective GPR40/FFA1 agonist (EC50 = 72 nM). It enhances glucose-dependent insulin secretion and improves hyperglycemia in type 2 diabetic rats. It has a Ki of 38 nM for the human GPR40 receptor. However, its clinical development was affected by findings of liver damage. It remains a valuable research tool for studying GPR40 biology.
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| Molecular Formula |
2[C29H32O7S].H2O
|
|---|---|
| Molecular Weight |
1067.26564
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| Exact Mass |
1066.38
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| Elemental Analysis |
C, 65.27; H, 6.23; O, 22.49; S, 6.01
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| CAS # |
1374598-80-7
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| Related CAS # |
Fasiglifam;1000413-72-8; 1374598-80-7 (hemihydrate);
1234474-57-7
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| PubChem CID |
57339446
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
12.724
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
75
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| Complexity |
828
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C(C2=CC(COC3=CC=C4[C@H](CC(O)=O)COC4=C3)=CC=C2)C(C)=CC(OCCCS(C)(=O)=O)=C1.CC5=C(C6=CC(COC7=CC=C8[C@H](CC(O)=O)COC8=C7)=CC=C6)C(C)=CC(OCCCS(C)(=O)=O)=C5.[H]O[H]
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| InChi Key |
OJXYMYYDAVXPIK-IWKNALKQSA-N
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| InChi Code |
InChI=1S/2C29H32O7S.H2O/c2*1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24;/h2*4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31);1H2/t2*23-;/m11./s1
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| Chemical Name |
2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid;hydrate
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| Synonyms |
Fasiglifam hemihydrate; 1374598-80-7; TAK-875 Hemihydrate; 8LDT91CH8A; 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid;hydrate;
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| HS Tariff Code |
2934.99.9001
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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 | 0.9370 mL | 4.6849 mL | 9.3697 mL | |
| 5 mM | 0.1874 mL | 0.9370 mL | 1.8739 mL | |
| 10 mM | 0.0937 mL | 0.4685 mL | 0.9370 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.
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