Varespladib (LY315920)
(Synonyms: 伐瑞拉迪; LY315920) 目录号 : GC17203
Inhibitor of group IIA, IIE, and X forms of sPLA2
Cas No.:172732-68-2
Sample solution is provided at 25 µL, 10mM.
IC50: 9 ± 1 nM or 7.3 x 10-6 mole fraction for sPLA2 activity
Phospholipases (PLAs) produce rate-limiting precursors in the various types of biologically active lipid biosynthesis. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. LY315920 was selected for evaluation clinically as an hnps-PLA2 inhibitor.
In vitro: The true potency of LY315920 was defined to be a mole fraction of 1.5 x 10-6 using a deoxycholate/phosphatidylcholine assay. LY315920 was found to be 40-fold less active against human, group IB, pancreatic sPLA2 and was inactive against cytosolic PLA2 and the constitutive and inducible forms of cyclooxygenase. Human sPLA2-induced thromboxane A2 release from isolated guinea pig lung bronchoalveolar lavage cells was inhibited by LY315920 with the IC50 of 0.79 μM [1].
In vivo: The i.v. administration of LY315920, 5 min before the bronchoalveolar lavage cells harvest, led to the inhibition of sPLA2-induced production of TXA2 with an ED50 of 16.1 mg/kg. [2].
Clinical trials: Varespladib methyl, an oral prodrug of LY-315920, effectively reduced LDL-C and inflammatory biomarkers in ACS patients treated with conventional atorvastatin therapy. There were no treatment differences in clinical cardiovascular events [2].
References:
[1] Snyder DW, Bach NJ, Dillard RD, Draheim SE, Carlson DG, Fox N, Roehm NW, Armstrong CT, Chang CH, Hartley LW, Johnson LM, Roman CR, Smith AC, Song M, Fleisch JH. Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999;288(3):1117-24.
[2] Rosenson RS, Hislop C, Elliott M, Stasiv Y, Goulder M, Waters D. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J Am Coll Cardiol. 2010;56(14):1079-88.
| Kinase experiment [1]: | |
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Chromogenic assay |
Varespladib was evaluated in the assay containing 0.96 mM racemic 1,2-bis(thioheptanoyl)-1,2-dideoxyphosphatidylcholine, 0.27 mM Triton X-100, and 0.12 mM 5,5’-dithiobis[2-nitrobenzoic acid] (DTNB). Concentration-response curves were generated with 16 nM recombinant human sPLA2 for 30 mins at 40 °C in a microtiter plate format. IC50 values were determined as well as mole fraction for 50% inhibition (Xi50). Mole fraction represented a dimensionless number derived by dividing the IC50 value by the concentration of lipid in the assay mixture. IC50 values were determined in triplicate. |
| Cell experiment [1]: | |
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Cell lines |
BAL cells |
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Preparation method |
The solubility of this compound in DMSO is > 8.175 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.1 ~ 3 μM |
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Applications |
In BAL cells stimulated with human sPLA2, Varespladib (0.1 ~ 3 μM) inhibited the formation of thromboxane in a concentration-dependent manner, with an IC50 value of approximately 8 × 10-7 M. In control experiments, Varespladib (3 μM) showed no effect on formyl-methionyl-leucyl-phenylalanine (a chemotactic peptide)-induced thromboxane release. Similarly, arachidonic acid-induced generation of thromboxane A2 was not inhibited by prior exposure to Varespladib. |
| Animal experiment [1]: | |
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Animal models |
Transgenic mice expressing human sPLA2 protein |
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Dosage form |
0.3 ~ 3 mg/kg; i.v. or p.o. |
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Applications |
In transgenic mice expressing human sPLA2 protein, Varespladib (0.3 ~ 3 mg/kg, i.v.) inhibited serum sPLA2 activity. However, the inhibition effect of Varespladib gradually decreased over the 4-hr observation period. Oral administration of Varespladib to transgenic mice leaded to similar dose-dependent inhibition on serum sPLA2 activity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Snyder DW, Bach NJ, Dillard RD, Draheim SE, Carlson DG, Fox N, Roehm NW, Armstrong CT, Chang CH, Hartley LW, Johnson LM, Roman CR, Smith AC, Song M, Fleisch JH. Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999;288(3):1117-24. | |
| Cas No. | 172732-68-2 | SDF | |
| 别名 | 伐瑞拉迪; LY315920 | ||
| 化学名 | 2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid | ||
| Canonical SMILES | CCC1=C(C2=C(N1CC3=CC=CC=C3)C=CC=C2OCC(=O)O)C(=O)C(=O)N | ||
| 分子式 | C21H20N2O5 | 分子量 | 380.39 |
| 溶解度 | ≥ 8.2 mg/mL in DMSO, ≥ 3.26 mg/mL in EtOH with ultrasonic and warming | 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 | 2.6289 mL | 13.1444 mL | 26.2888 mL |
| 5 mM | 0.5258 mL | 2.6289 mL | 5.2578 mL |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6289 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet