Work

A small molecule voltage-sensor modulator enhances the function of the cardiac NaV1.5 channel

Year: 2026

Type: article

Abstract: 1.5, but its recovery from inactivation was slowed. NZ-58 was able to bind to the channels in the closed state, not requiring the activated conformation of the VSDs, and it could exert its effects when applied from either side of the membrane. Being non-selective, NZ-58 is not an ideal lead compound for therapeutic ion channel modulation. However, considering that many clinically used ion channel modulators are multi-target "dirty drugs" that still achieve therapeutic benefit, and the unique features of its interactions with voltage-gated channels, we suggest that NZ-58 is worthy of further investigations as a prospective ion channel modulator lead compound.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2026.119530