Senicapoc (ICA-17043) is a potent inhibitor of the Gardos channel and ameliorates RBC dehydration in the SAD mouse. Senicapoc blocked Ca2+-induced rubidium flux from human RBCs with an IC50 value of 11 ± 2 nM (CLT IC50 = 100 ± 12 nM) and inhibited RBC dehydration with an IC50 of 30 ± 20 nM. Senicapoc is in treatment of Sickle Cell Disease and Sickle Cell Anemia

RBCs (human):11 ± 2 nM, RBC:30 ± 20 nM

ICA-17043 能够阻断小鼠（C57 Black）红细胞的 Gardos 通道，其 IC50 为 50±6 nM。ICA-17043 以浓度依赖的方式阻止了人类红细胞内血红蛋白浓度的增加[1]。

ICA-17043（10 mg/kg，口服）给药后，在第11天和第21天测量的Gardos通道活性显著降低，并且伴随红细胞K+含量的相应增加，而Na+含量未发生变化。ICA-17043（10 mg/kg，每天两次）在连续给药11天后，显著增加SAD小鼠的Hct水平[1]。Senicapoc（30 mg/kg，口服）在过敏原挑战后48小时取材的支气管肺泡灌洗液中减少嗜酸粒细胞数量，减轻气道高反应性和羊只的血管重塑[2]。

Senicapoc is dissolved in DMSO or 100% ethanol. 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.