IC50: 11 nM (Gardos channel)
ICA-17043 is shown to block the Gardos channel of mouse (C57 Black) RBCs with an IC 50 of 50±6 nM. ICA-17043 blocks this increase in cellular hemoglobin concentration in human RBCs in a concentration-dependent fashion.
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. 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.