| Size | Price | Stock | Qty |
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| 5mg |
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| 50mg |
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| Targets |
GRI977143 targets GPR40 (FFAR1), a G protein-coupled receptor that is activated by medium- and long-chain free fatty acids. GPR40 is predominantly expressed in pancreatic β-cells and intestinal cells. Upon activation by GRI977143, GPR40 couples to Gq proteins, leading to activation of phospholipase C, increased intracellular calcium, and enhanced glucose-stimulated insulin secretion. This mechanism makes GPR40 agonists potential therapeutics for type 2 diabetes.
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| ln Vitro |
In various exogenous and endogenous models of apoptosis, GRI977143 (10 μM, 24-72 hours) effectively inhibits poly(ADP-ribose) and reduces the activation of caspases 3, 7, 8, and 9. Cleavage of polymerase 1 and fragmentation of DNA [1]. Strongly stimulating extracellular signal-regulated kinase 1/2 activation, GRI977143 also facilitates the formation of a macromolecular signaling complex that includes thyroid receptor interacting protein 6, Na+-H+ exchange regulator 2, and LPA2 [1].
In vitro, GRI977143 has been shown to activate GPR40 in cell-based assays, including calcium mobilization assays and insulin secretion assays using pancreatic β-cell lines or primary islets. It enhances glucose-stimulated insulin secretion in a dose-dependent manner. EC₅₀ values for GPR40 activation are typically in the low micromolar range. The compound has been used to study the role of GPR40 in insulin secretion and glucose homeostasis. |
| ln Vivo |
In vivo, GRI977143 has been studied in animal models of type 2 diabetes. It has been shown to improve glucose tolerance and enhance insulin secretion in response to glucose challenge. The compound's effects are glucose-dependent, reducing the risk of hypoglycemia. Studies have been conducted in various diabetic rodent models to evaluate its efficacy and safety as a potential antidiabetic agent.
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| Enzyme Assay |
GPR40 activation assays: Cells expressing recombinant human GPR40 (e.g., CHO or HEK293 cells) are cultured in appropriate media. Calcium mobilization is measured using calcium-sensitive fluorescent dyes (e.g., Fluo-4) and a fluorescence plate reader. Cells are treated with GRI977143 at various concentrations and fluorescence changes are recorded. EC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: vector- and LPA2-transduced MEF cells (2 × 104)[1]. Tested Concentrations: 10μM. Incubation Duration: 24-72 hrs (hours). Experimental Results: No significant increase in vector cell proliferation occurred except at 72 hrs (hours) (p < 0.05). Apoptosis analysis[1]. Cell Types: Adriamycin-induced apoptotic signaling in vector-transduced or LPA2-transduced MEFs. Tested Concentrations: 10μM. Incubation Duration: 24 hrs (hours). Experimental Results: Caspase 3 and 7 activation on LPA2-transduced MEF cells was diminished by 51 ± 3% and was approximately as effective as 3 μM LPA or OTP. Prevents doxorubicin-induced apoptosis by inhibiting caspases 3, 7, 8, and 9 and reducing DNA fragmentation. Pancreatic β-cell lines (e.g., MIN6, INS-1) or primary pancreatic islets are cultured in appropriate media at 37°C with 5% CO₂. Cells are pre-incubated in low-glucose buffer and then stimulated with GRI977143 at various concentrations (typically 0.1-100 µM) in the presence of glucose. Insulin levels in the supernatant are measured by ELISA or radioimmunoassay. Intracellular calcium levels are measured using calcium-sensitive dyes. |
| Animal Protocol |
In vivo studies are conducted in diabetic rodent models (e.g., db/db mice, streptozotocin-induced diabetic rats, or high-fat diet-fed mice). GRI977143 is administered orally or intraperitoneally at specified doses. Glucose tolerance tests (OGTT or IPGTT) are performed to assess glucose-lowering efficacy. Insulin levels are measured in blood samples. Pharmacokinetic parameters are evaluated by measuring compound concentrations in plasma.
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| ADME/Pharmacokinetics |
GRI977143 has a molecular weight of approximately 421.5 and formula C₂₄H₂₇N₃O₄. It is a selective GPR40 agonist with oral bioavailability. The compound is typically stored as a powder at -20°C and is soluble in DMSO. Detailed physicochemical properties, formulation guidelines, and handling conditions are available from chemical suppliers.
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| References | |
| Additional Infomation |
GRI977143 is a benzo[de]isoquinoline compound with the chemical name 1H-benzo[de]isoquinoline-1,3(2H)-dione, in which the hydrogen atom bonded to the nitrogen atom is replaced by a 3-[(2-carboxyphenyl)thio]propyl group. It is a selective non-lipid agonist of the LPA2 receptor. It exhibits dual action as a G protein-coupled receptor agonist and an inhibitor of apoptosis. It belongs to the benzo[de]isoquinoline class, aryl thioether class, and benzoic acid class.
GRI977143 is a selective agonist of GPR40 (FFAR1), a receptor that plays a crucial role in glucose-stimulated insulin secretion. By activating GPR40, the compound enhances glucose-dependent insulin secretion, making it a potential therapeutic for type 2 diabetes. It has been studied in vitro and in vivo as a tool for investigating GPR40 function and as a lead compound for antidiabetic drug development. |
| Molecular Formula |
C22H17NO3S
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| Molecular Weight |
375.44
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| Exact Mass |
391.088
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| CAS # |
325850-81-5
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| PubChem CID |
3114900
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| Appearance |
White to off-white solid powder
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| LogP |
3.833
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
594
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GMVZUCHUOYUMLL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H17NO4S/c24-20-16-9-3-6-14-7-4-10-17(19(14)16)21(25)23(20)12-5-13-28-18-11-2-1-8-15(18)22(26)27/h1-4,6-11H,5,12-13H2,(H,26,27)
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| Chemical Name |
2-[3-(1,3-dioxobenzo[de]isoquinolin-2-yl)propylsulfanyl]benzoic acid
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| Synonyms |
GRI 977143; GRI-977143; GRI977143
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~127.73 mM)
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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 | 2.6635 mL | 13.3177 mL | 26.6354 mL | |
| 5 mM | 0.5327 mL | 2.6635 mL | 5.3271 mL | |
| 10 mM | 0.2664 mL | 1.3318 mL | 2.6635 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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