Researchers from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital have found a new method to increase both the speed and success rates of drug discovery.
The study, published Aug. 30 in the journal Advances in Scienceoffers renewed promise in new drug discovery.
“The hope is that we can accelerate the drug discovery timeline from years to months,” said Alex Thorman, PhD, co-first author and postdoctoral fellow in the Department of Environmental and Public Health Sciences in the College of Medicine.
The researchers combined two approaches to screen potential new drugs. First, they used a database from the Library of Integrated Network-based Cellular Signatures (LINCS) to simultaneously screen tens of thousands of small molecules with potential therapeutic effects. They then combined the search with targeted docking simulations used to model the interaction between small molecules and their protein targets to find compounds of interest. This accelerated the work schedule from months to minutes -? it takes weeks of work for the initial check to an afternoon.
Thorman said this faster method of screening for compounds that could become drugs speeds up the drug research process. But it’s not just speed that’s critical.
He added that this newer approach is more effective in identifying potentially effective compounds.
And the accuracy will only improve, hopefully offering new hope to many people who have diseases with no known cure, including those with cancer.”
Alex Thorman, PhD, co-first author
It may also create more targeted treatment options in precision medicine, an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environment and lifestyle.
“An accelerated drug discovery process could also be a game-changer in the ability to respond to public health crises such as the COVID-19 pandemic,” said Thorman. “Timeline for developing effective drugs could be accelerated.”
The other co-first authors were Jim Reigle, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital, and Somchai Chutipongtanate, PhD, an associate professor in the Department of Environmental and Public Health Sciences in the College of Medicine.
Corresponding authors of the study were Jarek Meller, PhD, professor of biostatistics, health informatics and data science in the College of Medicine, and Andrew Herr, PhD, professor of immunobiology in the Department of Pediatrics in the College of Medicine.
Other co-investigators were Mario Medvedovic, PhD, professor and director of the Center for Biostatistics and Bioinformatics Services at the College of Medicine, and David Hildeman, PhD, professor of immunobiology at the College of Medicine. Both Herr and Hildeman have research labs at Cincinnati Children’s Hospital.
This research was funded in part by grants from the National Institutes of Health, a Department of Veterans Affairs Merit Award, a UC Cancer Center Pilot Program Award, and a Cincinnati Children’s Hospital Innovation Fund Award.
Those involved in the research are also co-inventors of three US patents related to their work filed by Cincinnati Children’s Hospital.
Source:
Journal Reference:
Thorman, AW, et al. (2024) Accelerating drug discovery and repurposing by combining transcriptional signature connectivity with assocn.. Advances in Science. doi.org/10.1126/sciadv.adj3010.
