Senicapoc
(Synonyms: 4-氟-A-(4-氟苯基)-A-苯基-苯甲酰胺,ICA-17043) 目录号 : GC37628
An inhibitor of IKCa1/KCa3.1 channels
Cas No.:289656-45-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Senicapoc is an inhibitor of intermediate conductance calcium-activated potassium (IKCa1/KCa3.1) channels.1,2 It inhibits rubidium efflux from and dehydration of isolated human red blood cells (RBCs) induced by the calcium ionophore A23187 .1 Senicapoc (10 mg/kg twice per day) reduces IKCa1/KCa3.1 channel activity, increases potassium levels in RBCs, and decreases erythrocyte density in the SAD transgenic mouse model of sickle cell disease. It inhibits IL-2, IFN-γ, IL-12, and IL-17A production in CD3+ T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin when used at a concentration of 1 μM.3 Senicapoc (100 mg/kg) increases the paw withdrawal threshold in a rat model of chronic constriction injury (CCI) of the sciatic nerve.2
1.Stocker, J.W., De Franceschi, L., McNaughton-Smith, G.A., et al.ICA-17043, a novel gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD miceBlood101(6)2412-2418(2003) 2.Staal, R.G.W., Khayrullina, T., Zhang, H., et al.Inhibition of the potassium channel KCa 3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injuryEur. J. Pharmacol.7951-7(2017) 3.Hansen, L.K., Sevelsted-M?ller, L., Rabjerg, M., et al.Expression of T-cell KV1.3 potassium channel correlates with pro-inflammatory cytokines and disease activity in ulcerative colitisJ. Crohns Colitis8(11)1378-1391(2014)
Cell experiment: | The whole blood is initially diluted 1:1 with Modified Flux Buffer (MFB), consisting of 140 mM NaCl, 5 mM KCl, 10 mM Tris (tris(hydroxymethyl)aminomethane), 0.1 mM EGTA (ethyleneglycoltetraacetic acid) (pH=7.4). The blood is centrifuged at 1000 rpm, and the pellet comprised primarily of RBCs is washed 3 times with MFB. The cells are then loaded with 86Rb+ by incubating the washed cells with 86Rb+ at a final concentration of 0.185 MBq/mL (5 μCi/mL) in MFB for at least 3 hours at 37°C. After loading with 86Rb+, the RBCs are washed 3 times with chilled MFB. The cells are then incubated for 10 minutes with test compound (senicapoc) at concentrations that ranged from 1 nM to 10 000 nM. Efflux of 86Rb+ is initiated by raising intracellular calcium levels in the RBCs with the addition of CaCl2 and A23187 (a calcium ionophore) to final concentrations of 2 mM and 5 μM, respectively. After 10 minutes of incubation at room temperature, the RBCs are pelleted in a microcentrifuge, and the supernatant is removed and counted in a Wallac MicroBeta liquid scintillation counter. |
Animal experiment: | Transgenic Hbbsingle/single SAD1 (SAD) female and male mice between 3 and 6 months of age, weighing 25 to 30 g, are used for this study. The SAD mice are divided into 2 groups, and either vehicle (n=6) or senicapoc (10 mg/kg) (n=6) is administered orally by gavage twice daily. C57B6/2J mice are used as controls (wild-type mice). Hematologic parameters are evaluated at baseline and after 11 and 21 days of therapy. Blood sampling and vehicle administration have previously been shown not to affect the blood parameters measured in this study. |
References: [1]. Stocker JW, et al. ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood. 2003 Mar 15;101(6):2412-8. | |
| Cas No. | 289656-45-7 | SDF | |
| 别名 | 4-氟-A-(4-氟苯基)-A-苯基-苯甲酰胺,ICA-17043 | ||
| Canonical SMILES | O=C(C(C1=CC=CC=C1)(C2=CC=C(C=C2)F)C3=CC=C(F)C=C3)N | ||
| 分子式 | C20H15F2NO | 分子量 | 323.34 |
| 溶解度 | DMSO: 50 mg/mL (154.64 mM) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0927 mL | 15.4636 mL | 30.9272 mL |
| 5 mM | 0.6185 mL | 3.0927 mL | 6.1854 mL |
| 10 mM | 0.3093 mL | 1.5464 mL | 3.0927 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet