FR183998 free base
目录号 : GC33895
FR183998freebase是一种有效的Na+/H+-exchange抑制剂，通过测量在大鼠淋巴细胞、血小板及人血小板pHi值的变化中，得到IC50值分别为0.3nM，6.5nM和3.1nM。
Cas No.:239440-20-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Intracellular pH of rats lymphocytes is measured at 37°C with a spectrofluorometer by using the ratio of the emission (530 nm) obtained at 490- and 440-nm excitation wavelengths. After addition of 10 μL of the BCECF- and acid-loaded cells to 460 μL of Na-free buffer with 5 μL of DMSO or FR183998, 25 μL of 2.0 M NaCl (final 100 mM) is applied to start the reaction. The pHi change of cells is measured for >2 min. The initial increase in pHi in response to the added NaCl is taken as an estimate of Na+/H+-exchange activity, and the inhibitory effect of the drug is evaluated as IC50 value. The BCECF fluorescence signals are calibrated by titration with stepwise addition of small volumes of 1 M MES after permeabilization of the cells with 0.5% Triton X-100[1]. |
Animal experiment: | Male Sprague-Dawley rats age 9-10 weeks are anesthetized with sodium pentobarbital (50 mg/kg, i.p.), intubated, and ventilated with room air at a stroke volume of 4.5 mL with a frequency of 50 strokes/min. Saline or FR183998 is injected into the left femoral vein (bolus i.v.) 5 min before occlusion. Thoracotomy for coronary artery ligation is performed at the left side of the thorax above the heart, and the origin of the left anterior descending coronary artery is occluded by applying negative tension by aspiration through polyethylene tubing connected to the vacuum system, which can achieve regional ischemia. Successful occlusion is confirmed by ischemia-induced alteration of electrocardiogram (ECG). After 5-min ischemia, reperfusion is performed, and the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) of >5 s is observed intermittently over a 5-min period of reperfusion[1]. |
References: [1]. Ohara F, et al. Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion. J Cardiovasc Pharmacol. 1999 Dec;34(6):848-56. | |
FR183998 free base is a potent Na+/H+-exchange inhibitor, with IC50s of 0.3 nM, 3.1 nM and 6.5 nM by measurement of pHi change in rat lymphocytes, rat and human platelets, respectively.
FR183998 free base is a Na+/H+-exchange inhibitor, with IC50s of 0.3 nM, 6.5 nM and 3.1 nM by measurement of pHi change in rat lymphocytes, rat and human platelets, respectively[1].
FR183998 (0.1 and 1.0 mg/kg, i.v.) shows no effect hemodynamic parameters, and does not affect mean blood pressure and heart rate in conscious rats. Pretreatment of 0.01, 0.032, 0.10 mg/kg FR183998 or posttreament of 0.032 and 0.10 mg/kg FR183998 via intravenous administration, dose-dependently reuces reperfusion-induced ventricular fibrillation (VF) and mortality in reperfusion-induced arrhythmias in anesthetized rats, with ED50s against VF of 0.015 mg/kg and 0.070 mg/kg, respectively. FR183998 also reduces myocardial infarct sizes, and suppresses the arrhythmias in anesthetized rats[1]. FR183998 (1 mg/kg, i.v.) reduces the increase in serum levels of alanine transaminase, aspartate transaminase, and lactate dehydrogenase induced by hepatic I/R, and prevents the incidences of hepatic necrosis, apoptosis, and neutrophil infiltration. FR183998 blocks the I/R-induced activation of the NF-κB, reduces induction of iNOS and inhibits the production of nitric oxide. FR183998 also decreases the expression of the iNOS gene antisense transcript in the liver of hepatic I/R rats[2].
[1]. Ohara F, et al. Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion. J Cardiovasc Pharmacol. 1999 Dec;34(6):848-56. [2]. Ishizaki M, et al. Protective effect of FR183998, a Na+/H+ exchanger inhibitor, and its inhibition of iNOS induction in hepatic ischemia-reperfusion injury in rats. Shock. 2008 Sep;30(3):311-7.
| Cas No. | 239440-20-1 | SDF | |
| Canonical SMILES | O=C(C1=CC(C2=C(Cl)SC(Cl)=C2)=CC(C(NCCN(C)C)=O)=C1)NC(N)=N | ||
| 分子式 | C17H19Cl2N5O2S | 分子量 | 428.34 |
| 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 | 2.3346 mL | 11.673 mL | 23.3459 mL |
| 5 mM | 0.4669 mL | 2.3346 mL | 4.6692 mL |
| 10 mM | 0.2335 mL | 1.1673 mL | 2.3346 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。