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• W2576893313 abstract "Selective inhibition of Kv1.5, which underlies the ultra-rapid delayed rectifier current, IKur, has been pursued as a treatment for atrial fibrillation. Here we describe the discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity versus the off-target current IKs, whose inhibition has been associated with ventricular proarrhythmia. MK-1832 exhibits improved selectivity for IKur over IKs (>3000-fold versus 70-fold for MK-0448), consistent with an observed larger window between atrial and ventricular effects in vivo (>1800-fold versus 210-fold for MK-0448). MK-1832 also exhibits an improved preclinical pharmacokinetic profile consistent with projected once daily dosing in humans." @default.
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• W2576893313 date "2017-02-01" @default.
• W2576893313 modified "2023-09-27" @default.
• W2576893313 title "Discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity and pharmacokinetics" @default.
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• W2576893313 doi "https://doi.org/10.1016/j.bmcl.2016.12.054" @default.
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