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AM966

现货
Catalog No.
A3170
LPA1拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,940.00
现货
5mg
¥ 1,890.00
现货
10mg
¥ 3,280.00
现货
50mg
¥ 7,950.00
现货
200mg
¥ 15,550.00
现货

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Background

AM966 is a selective, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 17 and 19 nM for human or mouse LPA1, respectively [1]. Relative to LPA2, 3, 4, 5 receptors, AM966 shows 10-fold and 100-fold more selective in mouse and human cell lines for LPA1, respectively [1].

In vitro, AM966 shows to inhibit LPA-induced chemotaxis in IMR-90 human lung fibroblasts, A2058 human melanoma cells and CHO cells expressing LPA1 receptors [1].

In vivo, AM966 has been demonstrated to reduce total BALF cells, LDH activity, BALF collagen and total TGFβ concentrations in bleomycin-induced mice. Moreover, AM966 has been reported to block lung fibrosis, reduce lung inflammation and maintain body weight in mice induced by bleomycin [1].

Reference:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH, Seiders TJ,Parr TA, Prasit P, Evans JF, Lorrain DS.  A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010 Aug;160(7):1699-713.

文献引用

1. Li M, Lv Y, et al. "Co-stimulation of LPAR(1) and S1PR(1/3) increases the transplantation efficacy of human mesenchymal stem cells in drug-induced and alcoholic liver diseases." Stem Cell Res Ther. 2018 Jun 14;9(1):161. PMID:29898789
2. Cai J, Wei J, et al."AM966, an Antagonist of Lysophosphatidic Acid Receptor 1, Increases Lung Microvascular Endothelial Permeability through Activation of Rho Signaling Pathway and Phosphorylation of VE-Cadherin. Mediators Inflamm."2017;2017:6893560. PMID:28348461

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt490.93
Cas No.1228690-19-4
FormulaC27H23ClN2O5
SynonymsAM 966;AM-966
Solubility≥24.55 mg/mL in DMSO, ≥2.24 mg/mL in EtOH with ultrasonic and warming, <2.44 mg/mL in H2O
Chemical Name2-[4-[4-[4-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid
SDFDownload SDF
Canonical SMILESCC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

稳转人LPA1和小鼠LPA1的CHO细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

100%钙释放抑制:30分钟,100 nM;趋化性抑制:15分钟,IC50为469 nM,

实验结果

使用浓度逐渐增加的AM966预处理CHO细胞30分钟,然后用10-30 nM的LPA刺激并测量钙释放。在稳定表达人和小鼠LPA1受体的CHO细胞中,AM966抑制LPA刺激的细胞内钙释放。在稳定表达小鼠LPA1受体的CHO细胞中,评估AM966对LPA诱导的趋化性的抑制,IC50值为469 ± 54 nM。

动物实验[1]:

动物模型

雌性C57BL/6小鼠

剂量

口服,30 or 60 mg/kg,一天两次

实验结果

使用低剂量AM966(10 mg/kg)时未观察到肺纤维化的减少。然而,30和60 mg/kg的AM966显著减少肺组织重塑和纤维化,这些给药组中的肺结构与对照组相似。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Swaney J S, Chapman C, Correa L D, et al. A novel, orally active LPA1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. British journal of pharmacology, 2010, 160(7): 1699-1713.

生物活性

描述 AM966是一种高亲和性的、选择性的和可口服的LPA1受体(溶血磷脂酸受体)拮抗剂,IC50值为17 nM。
靶点 LPA1 receptor          
IC50 17 nM          

质量控制

化学结构

AM966

相关生物数据

AM966

相关生物数据

AM966