(691.5) Structure Activity Relationships of Illicit Fentanyl Analogs
Monday, April 4, 2022
10:00 AM – 12:00 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: B13
Sierra Moore (University of Michigan), Jess Anand (University of Michigan), Emma Dixon (University of Michigan), Carmelita Perrien-Naccarrato (University of Michigan), John Traynor (University of Michigan)
Fentanyl is a highly potent and efficacious mu opioid receptor (MOR) agonist with significant abuse potential. More than 70% of opioid overdose deaths involve fentanyl or one of its analogs; recently the DEA announced that 2 in 5 counterfeit prescription pills contain a lethal dose of fentanyl. However, little is known about the novel fentanyl analogs (fentalogs) flooding the illicit drug market. It is presumed that these novel fentalogs are also potent, highly efficacious MOR agonists and they are driving the increase in opioid overdoses, but pharmacological data on these compounds are scarce. We have determined the affinity for and agonist activity of a library of novel fentanyl analogs in vitro. We found that structure greatly alters affinity and agonist activity; in this library, affinity at MOR ranged from 0.4 nM to almost 400 nM – fentanyl displays 1.6 nM affinity for MOR. Based on the data collected from this library, we have been able to construct structure-activity relationships which may allow us to predict which fentalogs are potent agonists and are likely to carry significant abuse liability. Conversely, we have discovered new high affinity, low efficacy compounds which could be developed into novel rescue therapies.
Support or Funding Information
Supported by DA 048129, DA051723, and resources provided by the Edward F. Domino Research Center and Cayman Chemical.
Supported by lt;a href="https://projectreporter.nih.gov/project_info_details.cfm?aid=9720521amp;amp;icde=44122341amp;amp;ddparam=amp;amp;ddvalue=amp;amp;ddsub=amp;amp;cr=1amp;amp;csb=defaultamp;amp;cs=ASCamp;amp;pball=" title="Click to view Project Details"gt;DA 048129lt;/agt;, DA051723, and resources provided by the Edward F. Domino Research Center and Cayman Chemical.
