molecules of the month

The Genentech Nav1.7 inhibitor (GDC-0310) is a oral Ph. I clinical candidate for pain. Nav1.7 has been a hot target for pain, and we previously highlighted a Nav1.7 inhibitor as one of 2020’s Small Molecules of the Year. It is interesting among Nav1.7 inhibitors due to the presence of a very polar amine group where highly lipophilic elements were formerly incorporated, and is also an interesting example of an orally available zwitterion with a membrane-bound target. This acyl-sulfonamide derivative demonstrates >300-fold selectivity over Nav1.1, Nav1.5, and Nav1.6. Preclinical studies of GDC-0310 were conducted based on measuring its ability to block a response to aconitine (a plant alkaloid that causes abnormal opening of sodium channels). Unfortunately development of this molecule has…