NAEPA
(Synonyms: NAEPA, N-oleoyl ethanolamide phosphoric acid, OEA-P) 目录号 : GC44309An LPA mimetic and LPA receptor agonist
Cas No.:24435-25-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cas No. | 24435-25-4 | SDF | |
| 别名 | NAEPA, N-oleoyl ethanolamide phosphoric acid, OEA-P | ||
| Canonical SMILES | OP(OCCNC(CCCCCCC/C=C\CCCCCCCC)=O)(O)=O | ||
| 分子式 | C20H40NO5P | 分子量 | 405.5 |
| 溶解度 | Soluble in DMSO | 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 | 2.4661 mL | 12.3305 mL | 24.6609 mL |
| 5 mM | 0.4932 mL | 2.4661 mL | 4.9322 mL |
| 10 mM | 0.2466 mL | 1.233 mL | 2.4661 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Molecular basis for lysophosphatidic acid receptor antagonist selectivity
Biochim Biophys Acta 2002 May 23;1582(1-3):309-17.PMID:12069842DOI:10.1016/s1388-1981(02)00185-3.
Recent characterization of lysophosphatidic acid (LPA) receptors has made possible studies elucidating the structure-activity relationships (SAR) for agonist activity at individual receptors. Additionally, the availability of these receptors has allowed the identification of antagonists of LPA-induced effects. Two receptor-subtype selective LPA receptor antagonists, one selective for the LPA1/EDG2 receptor (a benzyl-4-oxybenzyl N-acyl ethanolamide phosphate, NAEPA, derivative) and the other selective for the LPA3/EDG7 receptor (diacylglycerol pyrophosphate, DGPP, 8:0), have recently been reported. The receptor SAR for both agonists and antagonists are reviewed, and the molecular basis for the difference between agonism and antagonism as well as for receptor-subtype antagonist selectivity identified by molecular modeling is described. The implications of the newly available receptor-subtype selective antagonists are also discussed.
Stereochemical properties of lysophosphatidic acid receptor activation and metabolism
Biochim Biophys Acta 2002 May 23;1582(1-3):295-308.PMID:12069841DOI:10.1016/s1388-1981(02)00184-1.
Ligand recognition by G protein-coupled receptors (GPCR), as well as substrate recognition by enzymes, almost always shows a preference for a naturally occurring enantiomer over the unnatural one. Recognition of lysophosphatidic acid (LPA) by its receptors is an exception, as both the natural L (R) and unnatural D (S) stereoisomers of LPA are equally active in bioassays. In contrast to the enantiomers of LPA, analogs of N-acyl-serine phosphoric acid (NASPA) and N-acyl-ethanolamine phosphoric acid (NAEPA), which contain a serine and an ethanolamine backbone, respectively, in place of glycerol, are recognized in a stereoselective manner. This stereoselective interaction may lead to the development of receptor subtype-selective antagonists. In the present study, we review the stereochemical aspects of LPA pharmacology and describe the chemical synthesis of pure LPA enantiomers together with their ligand-binding properties toward the LPA1, LPA2, and LPA3 receptors and their metabolism by lipid phosphate phosphatase 1 (LPP1). Finally, we evaluate the concept of stereopharmacology in developing novel ligands for LPA receptors.
Structure-activity relationships of lysophosphatidic acid analogs
Biochim Biophys Acta 2002 May 23;1582(1-3):289-94.PMID:12069840DOI:10.1016/s1388-1981(02)00183-x.
The physiologic effects of lysophosphatidic acid (LPA) remain poorly understood. Our ignorance is due in part to lack of medicinal chemistry focussed on this pleiotropic lipid mediator. Beginning with commercially available phospholipids tested on whole cells or tissues and continuing with synthetic analogs tested at recombinant LPA receptors, the features of the LPA pharmacophore have become visible. An active LPA mimetic has a long aliphatic chain terminating in a phosphate monoester; bulky substitutions at the second carbon (relative to the phosphate) are tolerated poorly and a dissociable proton near the phosphate group seems required for optimal activity. These requirements are met by substituting ethanolamine for the glyceryl group in LPA. Substitutions at the second carbon of the N-acyl ethanolamide phosphoric acid (NAEPA) result in highly active agonists, including some receptor type selective compounds, if the substituent is small (e.g. methyl, methylene amino, methylene hydroxy). However, bulky hydrophobic substituents lead to compounds with decreased agonist, or even antagonist, activities. Examination of naturally occurring plant lipids led to the discovery of another LPA receptor antagonist, di-octyl glyceryl pyrophosphate. An unexplained result obtained in testing the LPA mimetics is the strong stereoselectivity exhibited by some responses (e.g. calcium mobilization) and the lack of stereoselectivity of other responses (e.g. platelet aggregation).
Lysophosphatidic acid stimulates prostaglandin E2 production in cultured stromal endometrial cells through LPA1 receptor
Exp Biol Med (Maywood) 2009 Aug;234(8):986-93.PMID:19491366DOI:10.3181/0901-RM-36.
Lysophosphatidic acid (LPA) has been shown to be a potent modulator of prostaglandin (PG) secretion during the luteal phase of the estrous cycle in the bovine endometrium in vivo. The aims of the present study were to determine the cell types of the bovine endometrium (epithelial or stromal cells) responsible for the secretion of PGs in response to LPA, the cellular, receptor, intracellular, and enzymatic mechanisms of LPA action. Cultured bovine epithelial and stromal cells were exposed to LPA (10(-5)-10(-9) M), tumor necrosis factor alpha (TNFalpha; 10 ng/mL) or oxytocin (OT; 10(-7) M) for 24 h. LPA treatment resulted in a dose-dependent increase of PGE(2) production in stromal cells, but not in epithelial cells. LPA did not influence PGF(2alpha) production in stromal or epithelial cells. To examine which type of LPA G-protein-coupled receptor (LP-GPCR; LPA1, LPA2, or LPA3) is responsible for LPA action, stromal cells were preincubated with three selected blockers of LPA receptors: NAEPA, DGPP, and Ki16425 for 0.5 h, and then stimulated with LPA. Only Ki16425 inhibited the stimulatory effect of LPA on PGE(2) production and cell proliferation in the stromal cells. LPA-induced intracellular calcium ion mobilization was also inhibited only by Ki16425. Finally, we examined whether LPA-induced PGE(2) synthesis in stromal cells is via the influence on mRNA expression for the enzymes responsible for PGE(2) synthesis-PGE(2) synthase (PGES) and PG-endoperoxide synthase 2 (PTGS2). We demonstrated that the stimulatory effect of LPA on PGE(2) production in stromal cells is via the stimulation of PTGS2 and PGES mRNA expression in the cells. The overall results indicate that LPA stimulates PGE(2) production, cell viability, and intracellular calcium ion mobilization in cultured stromal endometrial cells via Ki16425-sensitive LPA1 receptors. Moreover, LPA exerts a stimulatory effect on PGE(2) production in stromal cells via the induction of PTGS2 and PGES mRNA expression.