Jeff Aube, the Fred Eshelman Distinguished Professor in the University of North Carolina's Department of Chemistry and School of Pharmacy, will deliver a seminar entitled, "New Opioid Biology Arising from Heterocyclic Chemistry." Hosted by Keith Woerpel.
For more information on Jeff Aube, click here.
Abstract: The worldwide opioid crisis has spurred efforts to develop new opioids for both existing uses (pain control) as well as new indications (itch, addiction). We have focused on the discovery of compounds able to selectively activate one of the two main intracellular pathways associated with the kappa opioid receptor. This type of activity, called “functional selectivity” or “ligand bias”, has the potential to segregate many of the ultimate biological effects of therapeutic opioids.
This project is an effort of a multidisciplinary, multi-institutional team led by the speaker and Professor Laura Bohn of the Scripps Research Institute. It began with the development of a speculative library for screening against a range of potential biological targets based on a known but underexplored isoquinolinone synthesis. Applying this chemistry to library synthesis led to a hit compound that stoked our interest in biased ligand discovery, ultimately leading to the discovery of Triazole 1.1, a strongly biased KOR agonist with a fascinating in vitro and in vivo profile. These efforts and recent results will be described.