This review explores the role of the Nav1.5 channel in cardiac diseases and evaluates SGLT2 inhibitors and novel compounds as potential late INa inhibitors for future therapeutic development.
This review summarizes the role of the Nav1.5 channel in cardiac diseases, the potential of SGLT2 inhibitors to interact with it, and future directions for developing late INa inhibitors using computational modeling.
ABSTRACT The Nav1.5 channel, a major isoform of voltage‐gated sodium ion channel, is mainly found in ventricular cardiomyocytes, playing a key role in generating essential cardiac action potentials for normal heart rhythms. Mutations in Nav1.5 have been associated with severe heart conditions such as long QT syndrome, Brugada syndrome, cardiac conduction disorders, atrial fibrillation, and dilated cardiomyopathy. Recent research has linked Nav1.5 to cardiac fibrosis and proposed its role in non‐cardiac illnesses, including specific neurological disorders and cancers, subjects that will be reviewed in this paper. On the other hand, sodium‐glucose cotransporter 2 inhibitors (SGLT2i), initially designed to manage diabetes by facilitating glucose excretion through urine, have demonstrated unexpected and encouraging cardioprotective benefits in clinical trials. This review compares the important SGLT2 inhibitors empagliflozin, dapagliflozin, and canagliflozin in terms of their interactions with Nav1.5 and their therapeutic effects on the heart. We also investigate new medications and compounds being developed to regulate Nav1.5 function, providing a preview of potential future treatments. Past attempts to develop late I Na inhibitors and difficulties in transitioning from the research phase to clinical trials have raised doubts about the optimal design of such trials. In addition, we cover the applications of molecular dynamics simulations in understanding the mechanism of action of these drugs within the Nav1.5 channel computationally. We hope that this review identifies new opportunities to generate more effective inhibitors using novel methods and advanced multiscale molecular modelling techniques.
Chattopadhyay et al. (Fri,) conducted a review in Cardiac conditions associated with Nav1.5 mutations. Late INa inhibitors and SGLT2 inhibitors was evaluated. This review explores the role of the Nav1.5 channel in cardiac diseases and evaluates SGLT2 inhibitors and novel compounds as potential late INa inhibitors for future therapeutic development.
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