University of Health Sciences and Pharmacy in St. Louis Researchers Published in the Journal of Medicinal Chemistry

Published on 08 December 2020

Researchers from University of Health Sciences and Pharmacy in St. Louis recently co-published a paper in the Journal of Medicinal Chemistry highlighting their work to uncover a compound that could play a key role in the future development of alternative therapeutics for pain management.

Susruta Majumdar, Ph.D., associate professor of Medicinal Chemistry at the University, and Abdelfattah Faouzi, Ph.D., postdoctoral research associate in the Center for Clinical Pharmacology, served as the lead authors on the paper, which represented a collaboration of more than 15 researchers from a variety of prestigious institutions including the Icahn School of Medicine at Mount Sinai, Memorial Sloan Kettering Cancer Center, Rutgers Robert Wood Johnson Medical School, University of Arizona Health Sciences College of Medicine Tucson and Washington University School of Medicine in St. Louis.

Over the past three years, the researchers have studied a series of carfentanyl amide-based opioid derivatives targeting the mu and delta opioid receptor complexes with the overall goal of identifying a safe, pharmacological agent with the ability to provide pain relief without the usual adverse side effects associated with conventional, clinical opioids, such as addiction and respiratory depression.

Through their work, the researchers uncovered a compound, known as MP135, which displays pharmacological characteristics that indicate it may be useful as a probe molecule which could be developed into an agent similar to morphine in mouse models, and may help to further understanding of opioid receptors.

“The important thing that we have discovered through this research is that we have a chemical probe to target receptor complexes,” said Majumdar. “In addition, we’ve also learned that receptor complexes may be the reason for the respiratory depression and addiction that occurs with morphine.”

With in vivo studies demonstrating side effects associated with MP135, research will continue to determine how to optimize this agent so it can be used for the development of future pain management therapeutics.

“On a promising note, we were able to identify an agent that was an analgesic in mice and more potent than morphine, but there are still some residual side effects that we are planning to examine further and better understand,” said Faouzi. “From here, we can optimize this agent to create an even more interesting compound with a better scientific profile, or we can create a better form of an existing pain medication that blocks side effects, while also maintaining the analgesia of morphine. We managed to get a lot of results from this work, and this is just the start of a highly collaborative project which will lead to further collaborations in the future.”

The full text of the study was published in the Nov. 25, 2020 issue of the Journal of Medicinal Chemistry. As a medicinal chemist himself, Faouzi notes that having this research published in such a reputed journal in the field marks an important milestone for him both personally and professionally.

“This was my first paper to be published in the Journal of Medicinal Chemistry, which is very important to me as an early-stage investigator, and also a testament to the tremendous work being done by our team in the Center for Clinical Pharmacology,” Faouzi explained. “This project was a great learning experience for me, and I was very grateful to have the opportunity to work on this exciting and highly collaborative project.”

For details about other exciting research projects happening at the University, visit uhsp.edu/research. To learn more about projects underway at the Center for Clinical Pharmacology, visit clinicalpharmstl.org.

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