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Potassium Channels: Structures, Diseases, and Modulators

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TLDR
This review tries to summarize the latest developments in structure determinants and regulation mechanism of all types of potassium channels and proves that modulators possess some certain natural‐product scaffolds and pharmacokinetic parameters are important properties for organic molecules.
Abstract
Potassium channels participate in many critical biological functions and play important roles in a variety of diseases. In recent years, many significant discoveries have been made which motivate us to review these achievements. The focus of our review is mainly on three aspects. Firstly, we try to summarize the latest developments in structure determinants and regulation mechanism of all types of potassium channels. Secondly, we review some diseases induced by or related to these channels. Thirdly, both qualitative and quantitative approaches are utilized to analyze structural features of modulators of potassium channels. Our analyses further prove that modulators possess some certain natural-product scaffolds. And pharmacokinetic parameters are important properties for organic molecules. Besides, with in silico methods, some features that can be used to differentiate modulators are derived. There is no doubt that all these studies on potassium channels as possible pharmaceutical targets will facilitate future translational research. All the strategies developed in this review could be extended to studies on other ion channels and proteins as well.

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References
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Journal ArticleDOI

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
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The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity

TL;DR: The architecture of the pore establishes the physical principles underlying selective K+ conduction, which promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.
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Natural Products as Sources of New Drugs over the Last 25 Years

TL;DR: This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003 and is able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame.
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A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel

TL;DR: The finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT, and that an additional subunit may be required for drug sensitivity.
Journal ArticleDOI

A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome

TL;DR: In this article, the authors investigated patients with long QT syndrome (LQT), an inherited disorder causing sudden death from a ventricular tachyarrythmia, torsade de pointes.
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