GRI 977143
目录号 : GC15865
GRI 977143是一种针对溶血磷脂酸受体2（LPA2 ）的非脂类激动剂，EC50值为3.3μM。
Cas No.:325850-81-5
Sample solution is provided at 25 µL, 10mM.
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GRI 977143 is a non-lipid agonist targeting the lysophosphatidic acid receptor 2 (LPA₂) with an EC50 value of 3.3μM[1]. It functions by mimicking the biological activity of the endogenous ligand lysophosphatidic acid (LPA), activating downstream LPA₂ signaling pathways, such as G protein-coupled cascades[2]. This activation subsequently regulates critical cellular processes including proliferation, migration, survival, and inflammatory responses[3].
In vitro, GRI 977143 (10μM) treatment for 24h significantly promoted the growth of LPA₂-transduced mouse embryonic fibroblast (MEF) cells[1]. In non-small cell lung cancer (NSCLC) cells, a 30min treatment with GRI 977143 (1μM) markedly enhanced resistance to cisplatin (CDDP), resulting in a significant increase in cell survival rate[4]. Furthermore, when MEF cells were exposed to 15 Gy γ-irradiation followed by 1h treatment with GRI 977143 (10μM), the compound effectively suppressed Caspase-9 expression and consequently attenuated γ-radiation-induced apoptosis[5].
In vivo, in an ovalbumin (OVA)-induced murine asthma model, a single intraperitoneal administration of GRI 977143 (1mg/kg) 30min prior to OVA sensitization significantly suppressed the elevation of eosinophil and lymphocyte levels[6].Daily intraperitoneal administration of GRI 977143 (3mg/kg) for four consecutive days activates lysophosphatidic acid receptor 2 (LPA₂), thereby ameliorating secretory diarrhea in myosin VB (MYO5B) knockout mice[7].
References:
[1] Kiss GN, Fells JI, Gupte R, Lee SC, Liu J, Nusser N, Lim KG, Ray RM, Lin FT, Parrill AL, Sümegi B, Miller DD, Tigyi G. Virtual screening for LPA2-specific agonists identifies a nonlipid compound with antiapoptotic actions. Mol Pharmacol. 2012 Dec;82(6):1162-73.
[2] Ishimoto K, Minami A, Minami K, Ueda N, Tsujiuchi T. Different effects of lysophosphatidic acid receptor-2 (LPA2) and LPA5 on the regulation of chemoresistance in colon cancer cells. J Recept Signal Transduct Res. 2021 Feb;41(1):93-98.
[3]Takai M, Mori S, Honoki K, Tsujiuchi T. Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cancer cell biology. J Bioenerg Biomembr. 2024 Aug;56(4):475-482.
[4]Ueda N, Minami K, Ishimoto K, Tsujiuchi T. Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells. Cell Signal. 2020 May;69:109551.
[5]Kiss GN, Lee SC, Fells JI, Liu J, Valentine WJ, Fujiwara Y, Thompson KE, Yates CR, Sümegi B, Tigyi G. Mitigation of radiation injury by selective stimulation of the LPA(2) receptor. Biochim Biophys Acta. 2013 Jan;1831(1):117-25.
[6]Lee YJ, Im DS. Efficacy Comparison of LPA2 Antagonist H2L5186303 and Agonist GRI977143 on Ovalbumin-Induced Allergic Asthma in BALB/c Mice. Int J Mol Sci. 2022 Aug 28;23(17):9745.
[7]Kaji I, Roland JT, Watanabe M, Engevik AC, Goldstein AE, Hodges CA, Goldenring JR. Lysophosphatidic Acid Increases Maturation of Brush Borders and SGLT1 Activity in MYO5B-deficient Mice, a Model of Microvillus Inclusion Disease. Gastroenterology. 2020 Oct;159(4):1390-1405.e20.
GRI 977143是一种针对溶血磷脂酸受体2（LPA2）的非脂类激动剂，EC50值为3.3μM[1]。它能够模拟天然配体溶血磷脂酸（LPA）的功能，激活LPA2下游的信号通路（如 G 蛋白偶联通路）[2]，从而调控细胞增殖、迁移、存活和炎症反应等过程[3]。
在体外，在LPA2转导的小鼠胚胎成纤维(MEF)细胞中，GRI 977143（10μM）处理细胞24h即可促进其生长[1]。GRI 977143（1μM）处理非小细胞肺癌（NSCLC）细胞30min，可显著提高NSCLC细胞对顺铂(CDDP)的抵抗力，细胞的存活率显著提高[4]。15 Gy γ照射小鼠胚胎成纤维MEF细胞后，用GRI 977143（10μM）处理MEF细胞1h，可抑制Caspase9的表达，从而减轻γ辐射诱导的细胞凋亡[5]。
在体内，在卵清蛋白（OVA）诱导的小鼠哮喘模型中，于OVA致敏前30min以1mg/kg剂量单次腹腔注射GRI 977143，可显著抑制嗜酸性粒细胞和淋巴细胞水平的升高[6]。连续四日每日腹腔注射GRI 977143（3mg/kg）可激活LPA2，从而改善肌球蛋白VB(MYO5B)基因敲除小鼠的分泌性腹泻症状[7]。
| Cell experiment [1]: | |
Cell lines | NSCLC cells |
Preparation Method | NSCLC cells were seeded into 96-well plates at a density of 5×10³ cells per well and cultured for 24h. Prior to initiating the cell viability assay, cells were pretreated with 10μM GRI 977143 for 30minutes. Subsequently, the cells were treated with varying concentrations (0, 1, 3, 5, 10, and 15μM) of cisplatin (CDDP) every 24h for two consecutive days. CCK-8 solution was added at 24 and 48h after treatment initiation, followed by an additional 2-hour incubation period before measuring the absorbance at 450nm using a microplate reader. |
Reaction Conditions | 10μM;30 minutes |
Applications | GRI 977143 (1μM) significantly enhanced the resistance of non-small cell lung cancer (NSCLC) cells to cisplatin, resulting in a marked increase in cell survival rate. |
| Animal experiment [2]: | |
Animal models | MYO5B-knockout mice |
Preparation Method | MYO5B knockout mice were randomly assigned to treatment groups (3-5 mice per group) and received daily intraperitoneal injections of GRI 977143 (3mg/kg) for 4 consecutive days. Tamoxifen-injected mice were used as control. On day 4, mice were euthanized, and samples were collected.The entire small intestine was collected for immunohistochemical and image analysis. |
Dosage form | 3mg/kg/day for 4days; i.p. |
Applications | Mice lacking MYO5B exhibit mislocalization of proteins in intestinal epithelial cells, leading to secretory diarrhea. GRI 977143 can activate lysophosphatidic acid (LPA) receptors, thereby reducing secretory diarrhea in MYO5B knockout mice. |
References: | |
| Cas No. | 325850-81-5 | SDF | |
| 化学名 | 2-[3-(1,3-dioxobenzo[de]isoquinolin-2-yl)propylsulfanyl]benzoic acid | ||
| Canonical SMILES | C1=CC=C(C(=C1)C(=O)O)SCCCN2C(=O)C3=CC=CC4=C3C(=CC=C4)C2=O | ||
| 分子式 | C22H17NO4S | 分子量 | 391.44 |
| 溶解度 | 10mg/mL in DMSO，10mg/mL in DMF | 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 | 2.5547 mL | 12.7733 mL | 25.5467 mL |
| 5 mM | 510.9 μL | 2.5547 mL | 5.1093 mL |
| 10 mM | 255.5 μL | 1.2773 mL | 2.5547 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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