ABC294640
(Synonyms: 3-(4-氯苯基)-N-(4-吡啶基甲基)金刚烷-1-甲酰胺,ABC294640) 目录号 : GC10154
An inhibitor of SPHK2
Cas No.:915385-81-8
Sample solution is provided at 25 µL, 10mM.
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ABC294640 is a selective and competitive inhibitor of sphingosine kinase 2 (SK2) with IC50 value of 60μM [1].
ABC294640 is a competitive inhibitor of SK2. It shows IC50 value of about 60μM against recombinant human SK2. In the kinetic assay, ABC294640 competes with sphingosine and exerts a Ki value of 9.8μM. Because of its targeting of the sphingosine binding site of SK2, ABC294640 shows no inhibition activity against other 20 kinases. In MDA-MB-231 cells, ABC294640 prevents S1P production with IC50 value of 26μM. Moreover, ABC294640 has anti-proliferation and anti-migration efficacies in tumor cells. It suppresses cell proliferation of a variety of tumor cell lines such as 1025LU, A-498, Caco-2 and HT-29. The IC50 values are ranged from 6μM to 48μM. Furthermore, administration of ABC294640 inhibits tumor growth in the immunocompetent BALB/c mice bearing mammary adenocarcimona xenografts. Besides that, ABC294640 is also found to have greater anti-proliferation effects in ER-positive than ER-negative breast cancer cells. The effect of E2 signaling caused by ABC294640 is expected to be a therapeutic in endocrine-related diseases [1, 2].
References:
[1] French K J, Zhuang Y, Maines L W, et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. Journal of Pharmacology and Experimental Therapeutics, 2010, 333(1): 129-139.
[2] Antoon J W, White M D, Meacham W D, et al. Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640. Endocrinology, 2010, 151(11): 5124-5135.
Cell experiment: | To determine the effects of the test compounds (e.g., Opaganib (ABC294640)) on proliferation, cells are plated into 96-well microtiter plates and allowed to attach for 24 h. Varying concentrations of Opaganib are added to individual wells and the cells are incubated for an additional 72 h. At the end of this period, the number of viable cells is determined by use of the sulforhodamine-binding assay. The percentage of cells killed is calculated as the percentage decrease in sulforhodamine-binding compare with control cultures. Regression analyses of inhibition curves are performed by use of GraphPad Prism[1]. |
Animal experiment: | Rats[1] Sprague-Dawley male rats (7-8 weeks old) are orally dosed with 0, 100, or 250 mg of ABC294640•HCl/kg in 0.375% Polysorbate-80 in PBS daily for 7 days. The animals are observed daily for viability, signs of gross toxicity, and behavioral changes, and a battery of detailed observations are performed on study days 1 and 7. Blood is sampled from all animals on day 8 of the study for hematology, clinical biochemistry, and serology assessments, and the animals are sacrificed. Gross necropsies are performed on all study rats, and selected organs and tissues are evaluated in the control and high-dose level groups. Mice[3] Male C57BL/6 (8-9 weeks) mice are gavaged with 50 mg/kg of Opaganib (ABC294640), or an equivalent volume of vehicle (0.375% Tween 80 in phosphate buffered saline, pH 7.1) 1 h before surgery. Under ether anesthesia, ischemia to 70% of the total liver is induced for 1 h. After opening the vascular clamp, the non-ischemic liver lobes are removed, and mice are observed 7 days for survival. Sham operation included equivalent anesthesia and laparotomy without ischemia. |
References: [1]. French KJ, et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. | |
| Cas No. | 915385-81-8 | SDF | |
| 别名 | 3-(4-氯苯基)-N-(4-吡啶基甲基)金刚烷-1-甲酰胺,ABC294640 | ||
| 化学名 | (7S)-3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide | ||
| Canonical SMILES | C1C2CC3(CC1CC(C2)(C3)C(=O)NCC4=CC=NC=C4)C5=CC=C(C=C5)Cl | ||
| 分子式 | C23H25ClN2O | 分子量 | 380.91 |
| 溶解度 | ≥ 38.1mg/mL 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 | 2.6253 mL | 13.1265 mL | 26.2529 mL |
| 5 mM | 0.5251 mL | 2.6253 mL | 5.2506 mL |
| 10 mM | 0.2625 mL | 1.3126 mL | 2.6253 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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet