生物活性

• 描述Senicapoc (ICA-17043) is a potent and selective Gardos channel (Ca2+-activated K+ channel; KCa3.1) blocker with an IC50 of 11 nM. Senicapoc blocks Ca2+-induced rubidium flux from human RBCs with an IC50 value of 11 nM and inhibits RBC dehydration with IC50 of 30 nM. Senicapoc is a potent inhibitor of the Gardos channel and ameliorates RBC (red blood cells) dehydration in the SAD mouse. Senicapoc is shown to block the Gardos channel of mouse (C57 Black) RBCs with an IC50 of 50 ± 6 nM. Senicapoc blocks this increase in cellular hemoglobin concentration in human RBCs in a concentration-dependent fashion. Senicapoc (10 mg/kg, twice a day) induces a significant increase in hematocrit (Hct) after 11 days of dosing in the sickle cell disease (SAD) mouse^[3]. 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. Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00102791	Sickle Cell Disease	Phase 3	Terminated(Because of the low ... more >>probability of achieving the primary endpoint.) Collapse <<	-	-
  NCT00294541	Sickle Cell Disease ... more >> Sickle Cell Anemia Collapse <<	Phase 3	Terminated(Lack of efficacy de... more >>monstrated in study ICA-17043-10) Collapse <<	-	-
  NCT00040677	Sickle Cell Disease ... more >> Sickle Cell Anemia Collapse <<	Phase 2	Completed	-	United States, Alabama ... more >> Study Site Birmingham, Alabama, United States United States, California Study Site Oakland, California, United States Study Site San Francisco, California, United States United States, District of Columbia Study Site Washington, District of Columbia, United States United States, Georgia Study Site Augusta, Georgia, United States United States, Illinois Study Site Chicago, Illinois, United States United States, Maryland Study Site Baltimore, Maryland, United States United States, Massachusetts Study Site Boston, Massachusetts, United States United States, Michigan Study Site Detroit, Michigan, United States United States, Mississippi Study Site Jackson, Mississippi, United States United States, New York Study Site Brooklyn, New York, United States Study Site New York, New York, United States United States, North Carolina Study Site Chapel Hill, North Carolina, United States Study Site Durham, North Carolina, United States United States, Pennsylvania Study Site Philadelphia, Pennsylvania, United States Study Site Pittsburgh, Pennsylvania, United States United States, Tennessee Study Site Nashville, Tennessee, United States United States, Texas Study Site Houston, Texas, United States United States, Virginia Study Site Richmond, Virginia, United States Collapse <<

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• 参考文献

• [1] Van Der Velden J, Sum G, 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.

  [2] Stocker JW, De Franceschi L, 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.

  [3] Stocker JW, De Franceschi L, McNaughton-Smith GA, Corrocher R, Beuzard Y, Brugnara C. ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood. 2003;101(6):2412-2418

  [4] Van Der Velden J, Sum G, Barker D, et al. K(Ca)3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma. PLoS One. 2013;8(6):e66886. Published 2013 Jun 24