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.
Highlights
The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (IKur ) current in cells [1], is an attractive familial atrial fibrillation (AF) type 7 drug target, because it is selectively expressed in the atria but not in the ventricles of human cells [2]
Variousand kinds of Kv1.5 modulators disclosed,with we summarize the molecular structures functionality of differenthave typesbeen of Kv1.5 modulators their chemical molecularasstructures and functionality of different modulators their chemical structure follows
(24) [23], resveratrol (52) [24], and correolide (55)). Application of these drugs may result in side effects related to the inhibition of Kv1.3 channels like immune suppression, more attention should be paid to the toxicity to hERG-related targets of Kv1.5 developing candidates
Summary
The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (IKur ) current in cells [1], is an attractive familial atrial fibrillation (AF) type 7 drug target, because it is selectively expressed in the atria but not in the ventricles of human cells [2]. We highlight recent advances in the discovery regard to the development of potential clinical candidates in the future From this perspective, we of small molecules as modulators of Kv1.5, and we discuss the structure-activity relationship (SAR). It is noteworthy that some inhibitors of Kv1.5 channels listed in Table 1 are not specific voltage-gated K+ channels for Kv1.5, and some of which block Kv1.3 channels (e.g., 4-aminopiridine (2), nifedipine (6), diltiazem (10), tetraethylammonium (11), propofol (24) [23], resveratrol (52) [24], and correolide (55)) Application of these drugs may result in side effects related to the inhibition of Kv1.3 channels like immune suppression, more attention should be paid to the toxicity to hERG-related targets of Kv1.5 developing candidates.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
