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AM095

现货
Catalog No.
A3166
有效的LPA1受体拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,150.00
现货
5mg
¥ 1,000.00
现货
10mg
¥ 1,400.00
现货
50mg
¥ 4,500.00
现货
200mg
¥ 9,500.00
现货

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Background

AM095 is a novel, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 0.73 and 0.98 μM for mouse or recombinant human LPA1, respectively [1].

In vitro, AM095 has shown to inhibit LPA1-induced chemotaxis of both mouse LPA1/CHO cells and human A2058 melanoma cells with IC50 values of 0.78 μM and 0.23μM [1].

In vivo, AM095 could dose-dependently block LPA-induced histamine release with an ED50 value of 8.3 mg/kg in mice. Additionally, AM095 has been revealed to remarkably reduce the BALF collagen and protein with an ED50 value of 10 mg/kg in lungs. AM095 has also shown to decrease both macrophage and lymphocyte infiltration induced by bleomycin in mice [1].

References:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Broadhead AR, Bain G, Santini AM, Darlington J, King CD, Baccei CS, Lee C, Parr TA, Roppe JR, Seiders TJ, Ziff J, Prasit P, Hutchinson JH, Evans JF, Lorrain DS. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. J Pharmacol Exp Ther. 2011 Mar;336(3):693-700.

文献引用

1. Harper K, R Lavoie R, et al. "The Hypoxic Tumor Microenvironment Promotes Invadopodia Formation and Metastasis through LPA1 Receptor and EGFR Cooperation." Mol Cancer Res. 2018 Jun 4. pii:molcanres.0649.2017. PMID:29866927
2. Szepanowski F, Szepanowski LP, et al. "Lysophosphatidic acid propagates post-injury Schwann cell dedifferentiation through LPA(1) signaling. Neurosci Lett." 2017 Oct 16;662:136-141. PMID:29051083
3. Banks DB, Chan GN, et al. "Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier." J Cereb Blood Flow Metab. 2018 May;38(5):857-868. PMID:28447863

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt478.47
Cas No.1345614-59-6
FormulaC27H23N2NaO5
SynonymsAM 095;AM-095
Solubility≥23.9 mg/mL in DMSO, ≥16.77 mg/mL in EtOH with ultrasonic, <2.49 mg/mL in H2O
Chemical Namesodium;2-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate
SDFDownload SDF
Canonical SMILESCC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)[O-].[Na+]
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

MDA-MB-231细胞和SK-OV3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

500 nM,5 min

实验结果

用AM-095或载体预处理细胞5分钟,然后用10 μM LPE或LPA处理。AM-095(500 nM)完全抑制两种细胞系中LPA诱导的[Ca2+]i应答和MDA-MB-231细胞中LPE诱导的[Ca2+]i应答。AM-095(500 nM)不影响SK-OV3细胞中LPE诱导的[Ca2+]i应答。

动物实验[2]:

动物模型

雌性CD-1小鼠

剂量

口服,1–30 mg/kg

实验结果

静脉内LPA(300 μg/mouse)攻击前2小时,给予小鼠10 ml/kg的AM095。LPA以剂量依赖性方式刺激组胺释放,在测试的最高浓度下引起接近14倍的刺激。AM095以剂量依赖性的方式抑制组胺释放,ED50为8.3 mg/kg,在30 mg/kg的剂量下最大减少80%。通过绘制组胺释放相对于每只动物的AM095血浆浓度的抑制百分比,假设最大响应为80%,我们计算得到EC50大约为1.5 μM。

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] Park S J, Lee K P, Im D S. Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells. Biomolecules & therapeutics, 2014, 22(2): 129.

[2] Swaney J S, Chapman C, Correa L D, et al. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. Journal of Pharmacology and Experimental Therapeutics, 2011, 336(3): 693-700.

生物活性

Description AM095是有效的LPA1受体拮抗剂,对重组人和小鼠LPA1的IC50值分别为0.98和0.73 μM。
靶点 LPA1 receptor          
IC50 0.98 μM (recombinant human) 0.73 μM (recombinant mouse)          

质量控制

化学结构

AM095

相关生物数据

AM095

相关生物数据

AM095

相关生物数据

AM095