Late I_Na as a Therapeutic Target: New Strategies, Computational Modelling, Drug Development, and Clinical Translation

Area of Science:

• Cardiovascular Science
• Pharmacology
• Molecular Biology

Background:

• The Nav1.5 channel is crucial for cardiac action potentials and its dysfunction causes heart conditions.
• Nav1.5 is implicated in cardiac fibrosis, neurological disorders, and cancers.
• Sodium-glucose cotransporter 2 inhibitors (SGLT2i) show cardioprotective effects beyond diabetes management.

Purpose of the Study:

• To review the role of Nav1.5 in cardiac and non-cardiac diseases.
• To compare SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) regarding their interaction with Nav1.5.
• To explore novel Nav1.5 modulators and computational methods for drug development.

Main Methods:

• Literature review of Nav1.5 channel function, mutations, and related diseases.
• Comparative analysis of SGLT2 inhibitors' effects on Nav1.5.
• Discussion of molecular dynamics simulations in understanding drug-channel interactions.

Main Results:

• Nav1.5 mutations are linked to various severe heart conditions.
• SGLT2 inhibitors exhibit promising therapeutic potential for heart conditions.
• Molecular dynamics simulations offer insights into drug mechanisms at the Nav1.5 channel.

Conclusions:

• Nav1.5 is a key target for cardiovascular therapeutics.
• SGLT2 inhibitors represent a novel therapeutic avenue for heart disease.
• Advanced computational techniques can accelerate the development of Nav1.5-targeting drugs.