This summer, Phil Cox, PhD, began research for a project his whole life’s work has led up to. As a principal investigator for drug metabolism research at Azusa Pacific University, Cox and three undergraduate students are collecting data in order to better understand how an antidepressant is metabolized by the human body.
Cox and his team are studying the mechanisms underlying the interaction of drugs and specific proteins in the liver. This interaction, called drug metabolism, can inform how often patients receive drug doses and the medication’s effectiveness. The research team is experimenting with the protein Cytochrome P450 2B6 and bupropion (an antidepressant). “In enzyme biochemistry, a protein attaches to something when its structures fit well with another,” Cox said, “similar to a puzzle piece, but much more complex and harder to take an image of.” Researchers don’t entirely know why 2B6 and specific drugs attach to each other, which is why Cox is using analogs—slightly modified bupropion structures—to find out if the protein still recognizes the drug’s makeup. “Will it attach more tightly? More loosely? In a different orientation? These are all questions that will guide us closer to understanding why 2B6 binds the way it does.” Discovering more about the nature of this protein could inform the way medical professionals develop these drugs and understand their dosages.
Biochemistry students Camille Campbell ’25 and Mark Tavoukjian ’25, as well as Biological Sciences student Natalie Turbedsky ’26 are making a significant contribution to the project through their meticulous practice, and overall enthusiasm to learn. They are gaining hands-on experience with industry standard equipment, using a liquid chromatography mass spectrometry (LC-MS) instrument. The assortment of clear tubes and purified liquids are more action-packed than one might think. The students use the LC-MS to perform targeted measurements and analysis of small molecules.
Cox had the idea to pursue this project last fall. “I’ve always been interested in the protein 2B6, and have done work in the past with analogs of a different drug. It was a natural next step for me to dive into another drug that fits so perfectly with the same protein,” he said. Research Triangle Institute (RTI) International agreed to share analogs they had developed of bupropion, and Cox started this specific project with bupropion at the beginning of this summer.
Recently, Cox submitted a grant proposal to the National Institutes of Health (NIH) titled “Probing the Structure Activity Relationship of Bupropion and Cytochrome P450 2B6.”
For Cox, the anticipated outcome is ultimately to provide scientists with a stronger understanding of drug metabolism so that administration can be done as effectively as possible. “We’re looking at how to inform the synthesis and creation of drugs with bupropion at the core of its structure,” he said. Cox’s research has the potential to make a significant contribution to drug metabolism studies.