GLPG0974 |
| Catalog No.GC31614 |
GLPG0974 is an oral, high-affinity, potent and selective free fatty acid receptor 2 (FFA2, GPR43, IC50 = 9nM) antagonist.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1391076-61-1
Sample solution is provided at 25 µL, 10mM.
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GLPG0974 is an oral, high-affinity, potent and selective free fatty acid receptor 2 (FFA2, GPR43, IC50 = 9nM) antagonist [1]. GLPG0974 inhibits neutrophil activation and migration by blocking the agonistic effect of short-chain fatty acids (SCFA) on FFA2, thereby exerting anti-inflammatory effects [2-3]. GLPG0974 is commonly used in inflammatory diseases [4].
In SH-SY5Y cells, treatment with GLPG0974 (100μM; 24h) significantly abolished the neuroprotective effect of a specific GPR43 agonist [5]. In myocardial cells, GLPG0974 (10μM; 5 minutes) prevents acetate-induced inhibition of myocardial contraction [6]. In IPEC-J2 cells, GLPG0974 (500nM; 24h) can restore PEDV replication in butyrate-pretreated IPEC-J2 cells [7].
In C57BL/6 mice, treated with GLPG0974 (1mg/kg; ig; 5 weeks) showed enhanced motor skills, increased numbers of fecal pellets, and significant improvement in constipation symptoms [8]. In the sepsis associated encephalopathy (SAE) mouse model established by cecal ligation and puncture (CLP) surgery, GLPG0974 (1mg/kg; po; 24d) can reverse the cognitive protective and anti-neuroinflammatory effects of short-chain fatty acids [9]. In high-fat-diet (HFD) fed mice model, abdominal fat in mice significantly increased after intragastric administration of GLPG0974 (1mg/kg; ig; 24d) [10].
References:
[1]. Namour F, Galien R, Van Kaem T, et al. Safety, pharmacokinetics and pharmacodynamics of GLPG0974, a potent and selective FFA2 antagonist, in healthy male subjects. British journal of clinical pharmacology. 2016 Jul; 82(1): 139-148.
[2]. Pizzonero M, Dupont S, Babel M, et al. Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: from hit to clinic. Journal of medicinal chemistry. 2014 Dec 11; 57(23): 10044-10057.
[3]. Wenzel TJ, Gates EJ, Ranger AL, et al. Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells. Molecular and Cellular Neuroscience. 2020 Jun 1; 105: 103493.
[4]. Vermeire S, Kojecky V, Knoflícek V, et al. GLPG0974, an FFA2 antagonist, in ulcerative colitis: efficacy and safety in a multicenter proof-of-concept study. J. Crohn’s Colitis. 2015 Feb 1; 9(Suppl 1): S39.
[5]. Saikachain N, Sungkaworn T, Muanprasat C, et al. Neuroprotective effect of short‐chain fatty acids against oxidative stress‐induced SH‐SY5Y injury via GPR43‐dependent pathway. Journal of Neurochemistry. 2023 Jul; 166(2): 201-214.
[6]. Jiang X, Zhang Y, Zhang H, et al. Acetate suppresses myocardial contraction via the short-chain fatty acid receptor GPR43. Frontiers in Physiology. 2022 Dec 16; 13: 1111156.
[7]. He H, Fan X, Shen H, et al. Butyrate limits the replication of porcine epidemic diarrhea virus in intestine epithelial cells by enhancing GPR43-mediated IFN-III production. Frontiers in microbiology. 2023 Jan 20; 14: 1091807.
[8]. Qu Y, An K, Wang D, et al. Short-Chain Fatty Acid Aggregates Alpha-Synuclein Accumulation and Neuroinflammation via GPR43-NLRP3 Signaling Pathway in a Model Parkinson’s Disease. Molecular Neurobiology. 2025 Feb 4: 1-4.
[9]. Li H, Bao H, Jiang L, et al. Short chain fatty acids protect the cognitive function of sepsis associated encephalopathy mice via GPR43. Frontiers in Neurology 13: 909436 [Internet]. 2022
[10]. Pham MT, Tran TD, Zayabaatar E. Leuconostoc mesenteroides utilizes glucose fermentation to produce electricity and ameliorates high-fat diet-induced abdominal fat mass. Archives of Microbiology. 2022 Nov; 204(11): 670.
| Cell experiment [1]: | |
Cell lines | SH-SY5Y cells |
Preparation Method | SH-SY5Y cells were seeded on a 96-well culture plate at a seeding density of 2.5 × 104 cells/well. All the cells were randomly incubated with various conditions of short-chain fatty acids (SCFAs) mixture, propionate, and butyrate, 10nM GPR43 agonist (butanamide), and some experiments were combined with 100μM GPR43 antagonist (GLPG0974) or 5μM PLC inhibitor (U73122) in culture medium for 24h. |
Reaction Conditions | 100μM; 24h |
Applications | Pretreatment with a GPR43 antagonist (GLPG0974) significantly abolished the neuroprotective effect of a specific GPR43 agonist. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Forty mice were used to further examine short-chain fatty acids (SCFA)-induced NLRP3 inflammasome activation under four experimental conditions: control, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), MPTP + SCFA, and MPTP + SCFA with a GPR43 inhibitor (GLPG0974). (1) The control group received 0.9% saline and regular drinking water; (2) the MPTP group received 18mg/kg MPTP in divided doses every two weeks for 5 weeks; (3) the MPTP + SCFAs group received the same MPTP treatment plus water supplemented with SCFAs; (5) the MPTP + SCFAs + GLPG0974 group, GLPG0974 at a dose of 1mg/kg, 3 times a week for 5 weeks. |
Dosage form | 1mg/kg; ig; 3 times a week for 5 weeks |
Applications | Mice treated with GLPG0974 showed enhanced motor skills, increased numbers of fecal pellets, and significant improvement in constipation symptoms. |
References: | |
| Cas No. | 1391076-61-1 | SDF | |
| Chemical Name | 4-[[[(2R)-1-(benzo[b]thien-3-ylcarbonyl)-2-methyl-2-azetidinyl]carbonyl][(3-chlorophenyl)methyl]amino]-butanoic acid | ||
| Canonical SMILES | O=C(O)CCCN(C([C@]1(C)N(C(C2=CSC3=CC=CC=C32)=O)CC1)=O)CC4=CC=CC(Cl)=C4 | ||
| Formula | C25H25ClN2O4S | M.Wt | 485 |
| Solubility | DMSO : 200 mg/mL (412.37 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0619 mL | 10.3093 mL | 20.6186 mL |
| 5 mM | 0.4124 mL | 2.0619 mL | 4.1237 mL |
| 10 mM | 0.2062 mL | 1.0309 mL | 2.0619 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)
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