W146
目录号 : GC16621
A selective S1P1 receptor antagonist
Cas No.:909725-61-7
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
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Cell experiment: |
Endothelial progenitor cells (EPCs) proliferation is examined by the colorimetric MTS assay. EPCs are seeded in 96-well plates in quintuplicate at a density of 1×104/well and cultured in synchronized DMEM/H (supplemented with 0.5% bovine serum albumin (BSA), and lacking fetal bovine serum (FBS) and endothelial cell growth supplement (ECGS)). After culturing for 12 h, EPCs are incubated in 20% FBS-supplemented DMEM/H with S1P (0, 200, 800, and 1,400 nM). MTS (20 mL/well) is added into the culture medium to incubate for another 8 hrs at 37°C. The optical density (OD) at 490 nm is recorded using a 96-well plate reader. The potent S1PR1 antagonists like W146 (10 μM), and S1PR3 antagonists are added into culture medium for 30 min before the addition of S1P. Simultaneously, cells are counted by detecting the effect of S1P treatment on EPC proliferation[2]. |
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Animal experiment: |
Mice[3]Mice (4-6-week-old) are used. All mice go through 2-week adaptation period and are used for experiments at 6-8 weeks of age. Mice are IP injected with W146, and measured for Kit+/Sca-1+/Lin- hematopoietic stem progenitor cells (KSL-HSPC) mobilization by CFU-G/M analysis. Flow cytometry analysis of blood samples from mice pretreated with 5 mg/kg of body weight W146, W140, JTE013, or Cay10444, followed by AMD3100 (ADM) administration. Mice injected with W140 (an inactive enantiomer of W146), JTE013 (S1P2 selective antagonist), or Cay10444 (S1P3 selective antagonist) are used as controls[3]. |
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References: [1]. M Germana Sanna, et al. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006 Aug;2(8):434-41. Epub 2006 Jul 9. |
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W146 is a selective antagonist of sphingosine-1-phosphate receptor 1 (S1PR1) with an EC50 value of 398 nM.
W146 is a S1PR1 antagonist with a Ki of ~70-80 nM[1]. Compared with the S1P treated group, the S1P attenuated TUNEL labeling index of EPCs is significantly increased by pretreatment with W146. Furthermore, pretreatment with W146 significantly increases activated cleaved caspase-3 levels. The reduced EPCs apoptosis which induced by S1P is completely abolished after treatment with W146[2].
Injections of W146, W140, JTE013, or Cay10444 do not alter the basal WBC count in mice. It is found that a significant increase in KSL-HSPC mobilization when mice are pretreated with W146, compared to that in mice pretreated with dextran followed by AMD3100 administration. Moreover, pre-treatment of W146 shows approximately 8-fold increase of KSL-HSPC mobilization, measured by the CFU-G/M colony forming assays, compared to that in mice treated with AMD3100 alone. The W146-mediated augmentation of KSL-HSPC mobilization is specific, because pretreatment of mice with W140 is unable to produce any effect on AMD3100-stimulated KSL-HSPC mobilization[3].
References:
[1]. M Germana Sanna, et al. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006 Aug;2(8):434-41. Epub 2006 Jul 9.
[2]. Hang Wang, et al. Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway. Cell Biol Int. 2018 May 23.
[3]. Jingjing Liu, et al. 3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals. J Biochem Pharmacol Res. 2013 Dec; 1(4): 197–203.
| Cas No. | 909725-61-7 | SDF | |
| 化学名 | (R)-(3-amino-4-((3-hexylphenyl)amino)-4-oxobutyl)phosphonic acid | ||
| Canonical SMILES | OP(O)(CC[C@H](C(NC1=CC(CCCCCC)=CC=C1)=O)N)=O | ||
| 分子式 | C16H27N2O4P | 分子量 | 342.37 |
| 溶解度 | 3eq. NaOH: 6.85mg/mL (20mM) | 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 | 2.9208 mL | 14.6041 mL | 29.2082 mL |
| 5 mM | 0.5842 mL | 2.9208 mL | 5.8416 mL |
| 10 mM | 0.2921 mL | 1.4604 mL | 2.9208 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。