A Drug Discovery Approach for an Effective Pain Therapy through Selective Inhibition of Nav1.7.

ABSTRACT: Chronic pain is a widespread disorder affecting millions of people and is insufficiently addressed by current classes of analgesics due to significant long-term or high dosage side effects. A promising approach that was recently proposed involves the systemic inhibition of the voltage-gated sodium channel Nav1.7, capable of cancelling pain perception completely. Notwithstanding numerous attempts, currently no drugs have been approved for the inhibition of Nav1.7. The task is complicated by the difficulty of creating a selective drug for Nav1.7, and avoiding binding to the many human paralogs performing fundamental physiological functions. In our work, we obtained a promising set of ligands with up to 5-40-fold selectivity and reaching 5.2 nanomolar binding affinity by employing a proper tr

SUBMITTER: Trombetti GA 

PROVIDER: S-EPMC9223482 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature