NaV1.7 Inhibitor Roundup: From Broad-Spectrum to Subtype-Selective Clinical Candidates

The discovery that individuals with null mutations in the NaV1.7 channel exhibited pain insensitivity sparked industry interest in targeting NaV1.7 to potentially treat chronic pain without major side effects. Despite the potential of selectively inhibiting sodium channels like NaV1.7, NaV1.8, and NaV1.9 for pain management, developing selective inhibitors suitable for clinical use has proven challenging over the past two decades. This article complements our recent coverage of VX-548, review of NaV1.8 as a critical target in pain management, and our NaV1.8 compound roundup and provides a historical reminder of noteworthy preclinical and clinical NaV1.7 small molecule inhibitors as of April 2024.