Clark-Led Partnership Aims to Deliver Safer, Better Tolerated Drugs
Joseph Clark, assistant professor of chemistry at the University of Tennessee, Knoxville, recently published new research describing a method for precision control of the structure of deuterated compounds, which could impact future drug discovery as it relates to patient health.
Deuterium is a naturally occurring isotope of hydrogen that is being leveraged in drug development as either a means to improve existing drugs, or discover new drug candidates. Deuterated molecules are created by replacing a hydrogen atom with a deuterium atom. The resulting molecule is often more stable and can have several pharmaceutical benefits.
Clark's research is focused on the construction and investigation of organic molecules. Likening this work to that of an architect, he compares finding the best position for atoms in a molecule to identifying the best placement for a window in a building. There may be multiple positions that create an effective drug, but being able to control the placement of specific atoms can help identify the best possible version of that drug.
"What we can do in drug discovery is swap out a molecule's hydrogen for a deuterium, and if we can select the deuterium's position in that drug molecule, we can build a better drug with fewer potential side effects," said Clark. He added that this can lead to better health outcomes as patients may no longer have to decide between treating their condition and managing any undesirable effects of the treatment.
Clark's recent publication focuses on a new means of controlling the placement of deuterium within a molecule. His team worked with Brooks Pate, MacArthur Fellow and chemistry professor at the University of Virginia, to develop an academic-industry collaboration that includes Vertex Pharmaceuticals and BrightSpec Inc.
Vertex Pharmaceuticals is responsible for the drug Alyftrek, an FDA-approved deuterated drug used to treat cystic fibrosis. Working with Vertex provided Clark's team with valuable insight into the organization's creation and use of deuterated molecules.
"We had this idea that you could take allenes, which is a common functional group in organic chemistry and transform those into these highly valuable deuterated products," said Clark. "We were approached by Vertex Pharmaceuticals to collaborate on this project, and we saw a lot of value in the resources and experience they could bring in deuterated drug discovery."
Lihan Qi, a graduate student in Clark's research group and co-author of the publication, worked closely with their industry partners, carrying out the group's research in the laboratories of Vertex Pharmaceuticals.
A recently awarded NIH grant provided an opportunity for Clark's team to engage the expertise of a second industry partner; BrightSpec Inc. BrightSpec specializes in instrumentation using molecular rotational resonance spectroscopy (MRR), which allows for the rapid characterization of the unique 3 dimensional structure of small molecules.
"Working with BrightSpec has brought an aspect of innovation to the research that we couldn't have envisioned prior to collaborating with them. Instrumentation developed by BrightSpec allowed us to characterize and quantify all the isotopic species in our reactions. We were then able to leverage the expertise of our academic collaborators on Dr. Pate's team and BrightSpec in conjunction with our new instrumentation to perform the research," said Clark. Clark and his team worked closely with their partners, creating a unique collaboration that paired academic expertise with real-time, ongoing industry input. The resulting research provides a critical new tool for the future of safe, effective drug development.
Provided by University of Tennessee at Knoxville
