Hannah Stewart
Pronouns: she/her
Research Mentor(s): Mengchu Li
Research Mentor School/College/Department: Pharmacology / Medicine
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Hannah Stewart, Jason Rech, Mengchu Li, John Traynor
Abstract
Presently, opioid use disorder (OUD) affects over 2.1 million people in the United States.1 Opioid agonists that target the µ-opioid receptor (MOR) are effective pain management medications but can adversely lead to dependence, addiction, and an array of negative side effects. Current FDA-approved treatments for OUD include orthosteric agonists and antagonists, however, these treatments are quite limited in their scope due to their orthosteric characteristics. Therefore, it is of particular interest to identify novel compounds that could potentially be acting as negative allosteric modulators (NAMs) and prevent the binding of opioid agonists at the orthosteric site of the MOR independent of the opioid agonist concentration. In the current study, 15 novel compounds were tested by performing a GTP?35S radioactive binding assay to measure their in vitro potency. Potency was measured by creating a dose-response curve (DRC) and evaluating the half-maximal inhibitory concentration (IC50). Previously, one lead compound was identified as a NAM and has an IC50 of 10 nM. In our study, one compound has been identified to have a higher potency than the lead compound by fivefold. In the future, this compound will be analyzed to verify its allosteric identity, and in vivo experiments will be performed. These data are valuable for informing future drug design to create compounds that can begin the clinical trial process and combat opioid use disorder. 1. Dydyk, A. M., Jain, N. K., & Gupta, M. Opioid Use Disorder. National Library of Medicine. 2022 Jun.
