molecules of the month

Context. ABBV-318 (AbbVie) is a CNS-penetrating, oral inhibitor of Nav1.7/Nav1.8 being developed for pain treatment. Despite being a highly validated pain target due to its important role in excitable cells, Nav1.7 inhibition has not lived up to its potential, and translation of the promising preclinical observations to human studies has been elusive. A close isoform, Nav1.8, which has mostly encountered similar fates (e.g. XEN-402) in preclinical and clinical studies as Nav1.7, has recently entered the spotlight following a Ph. II readout from Vertex that reported positive data for the Nav1.8 inhibitor VX-548 (structure undisclosed, but related to prodrug VX-150). Similar to Nav1.7, Nav1.8 has been implicated as a key mediator of inflammatory pain, suggesting that a dual Nav1.7/Nav1.8 inhibitor may…