The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity.
نویسندگان
چکیده
Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development.
منابع مشابه
Gardos pathway to sickle cell therapies?
In this issue of Blood, Ataga and colleagues report that treatment of sickle cell disease patients with senicapoc, a Gardos channel inhibitor, reduces the number of dehydrated cells, increases hemoglobin levels, and diminishes hemolysis.
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A prominent feature of sickle cell anemia is the presence of dehydrated red blood cells (RBCs) in circulation. Loss of potassium (K(+)), chloride (Cl(-)), and water from RBCs is thought to contribute to the production of these dehydrated cells. One main route of K(+) loss in the RBC is the Gardos channel, a calcium (Ca(2+))-activated K(+) channel. Clotrimazole (CLT), an inhibitor of the Gardos ...
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It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using (86)Rubidium ((86)Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activat...
متن کاملRED CELLS Modulation of Gardos channel activity by cytokines in sickle erythrocytes
It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using 86Rubidium (86Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation ...
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عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 60 1 شماره
صفحات -
تاریخ انتشار 2016