Senicapoc (Synonyms: ICA-17043) |
| Catalog No.GC37628 |
An inhibitor of IKCa1/KCa3.1 channels
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 289656-45-7
Sample solution is provided at 25 µL, 10mM.
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Senicapoc (ICA-17043) is a potent and selective Gardos channel blocker with IC50 value of 11 nM. It blocks Ca2+-induced rubidium flux from human RBCs with an IC50 value of 11 nM and inhibits RBC dehydration with IC50 of 30 nM. IC50: 11 nM (Gardos channel)
ICA-17043 is shown to block the Gardos channel of mouse (C57 Black) RBCs with an IC50 of 50±6 nM. ICA-17043 blocks this increase in cellular hemoglobin concentration in human RBCs in a concentration-dependent fashion[1].
ICA-17043 (10 mg/kg, p.o.) administration produces a significant decrease in Gardos channel activity measured at day 11 and 21 and is associated with a corresponding increase in red cell K+ content without changes in Na+ content. ICA-17043 (10 mg/kg, twice a day) induces a significant increase in Hct after 11 days of dosing in the SAD mouse[1]. Senicapoc (30 mg/kg, p.o.) reduces airway hyperresponsiveness, eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and vascular remodelling in the sheep[2].
[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. [2]. Van Der Velden J, et al. K(Ca)3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma. PLoS One. 2013 Jun 24;8(6):e66886. [3]. Staal RG, et al. Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury. Eur J Pharmacol. 2017 Jan 15;795:1-7.
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 | |
| Synonyms | ICA-17043 | ||
| Canonical SMILES | O=C(C(C1=CC=CC=C1)(C2=CC=C(C=C2)F)C3=CC=C(F)C=C3)N | ||
| Formula | C20H15F2NO | M.Wt | 323.34 |
| Solubility | DMSO: 50 mg/mL (154.64 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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- Purity: >99.50%
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Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)
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