GLPG0974
目录号 : GC31614GLPG0974是一种口服、高亲和力、强效且选择性的游离脂肪酸受体2（FFA2, GPR43，IC50 = 9nM）拮抗剂。
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.
GLPG0974是一种口服、高亲和力、强效且选择性的游离脂肪酸受体2（FFA2, GPR43，IC50 = 9nM）拮抗剂 [1]。GLPG0974通过阻断短链脂肪酸（SCFA）对FFA2的激动作用来抑制中性粒细胞活化和迁移，从而发挥抗炎作用 [2-3]。GLPG0974常用于治疗炎症性疾病 [4]。
在SH-SY5Y细胞中，GLPG0974（100μM；24h）处理可显著消除特定GPR43激动剂的神经保护作用 [5]。在心肌细胞中，GLPG0974（10μM；5分钟）可阻止醋酸盐诱导的心肌收缩抑制 [6]。在IPEC-J2细胞中，GLPG0974（500nM；24h）可恢复经丁酸预处理的IPEC-J2细胞中PEDV的复制 [7]。
在C57BL/6小鼠中，用GLPG0974（1mg/kg；ig；5周）治疗后，小鼠的运动技能增强，粪便颗粒数量增加，便秘症状显著改善 [8]。在通过盲肠结扎穿刺（CLP）手术建立的脓毒症相关性脑病（SAE）小鼠模型中，GLPG0974（1mg/kg；po；24d）可逆转短链脂肪酸的认知保护和抗神经炎作用 [9]。在高脂饮食（HFD）喂养的小鼠模型中，小鼠灌胃GLPG0974（1mg/kg；ig；24d）后，腹部脂肪显著增加 [10]。
| 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 | |
| 化学名 | 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 | ||
| 分子式 | C25H25ClN2O4S | 分子量 | 485 |
| 溶解度 | DMSO : 200 mg/mL (412.37 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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