Hydraphiles are a class of synthetic ion channels that now have a twenty-year history of analysis and success. In early studies,\r\nthese compounds were rigorously validated in a wide range of in vitro assays including liposomal ion ??ow detected by N??R\r\nor ion-selective electrodes, as well as biophysical experiments in planar bilayers. During the past decade, biological activity was\r\nobserved for these compounds including toxicity to bacteria, yeast, and mammalian cells due to stress caused by the disruption of\r\nion homeostasis. ?e channel mechanism was veri??ed in cells using membrane polarity sensitive dyes, as well as patch clamping\r\nstudies. ?is body of work has provided a solid foundation with which hydraphiles have recently demonstrated acute biological\r\ntoxicity in the muscle tissue of living mice, as measured by whole animal ??uorescence imaging and histological studies. Here we\r\nreview the critical structure-activity relationships in the hydraphile family of compounds and the in vitro and in cellulo experiments\r\nthat have validated their channel behavior. ?is report culminates with a description of recently reported efforts in which these\r\nmolecules have demonstrated activity in living mice.
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