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Updated: Jan 1, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5
Zefeng Zhao1,2, Songsong Ruan1,2, Xiaoming Ma1,2
1Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, 229 Taibai Road, Xi'an 710069, China.
Abstract:
The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (IKur) current in human cells, has a crucial role in atrial fibrillation. Therefore, the design of selective Kv1.5 modulators is essential for the treatment of pathophysiological conditions involving Kv1.5 activity. This review summarizes the progress of molecular structures and the functionality of different types of Kv1.5 modulators, with a focus on clinical cardiovascular drugs and a number of active natural products, through a summarization of 96 compounds currently widely used. Furthermore, we also discuss the contributions of Kv1.5 and the regulation of the structure-activity relationship (SAR) of synthetic Kv1.5 inhibitors in human pathophysiology. SAR analysis is regarded as a useful strategy in structural elucidation, as it relates to the characteristics that improve compounds targeting Kv1.5. Herein, we present previous studies regarding the structural, pharmacological, and SAR information of the Kv1.5 modulator, through which we can assist in identifying and designing potent and specific Kv1.5 inhibitors in the treatment of diseases involving Kv1.5 activity.
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