The general principle of the novel connectivity-enhanced structure-activity relationship (ceSAR) approach that ranks candidate molecules based on their similarity to LINCS analogues with signatures consistent with those of the target gene KDs (left panel), and can then be combined with docking simulations to assess shape complementarity with specific protein targets (right panel). Credit: Alexander Thorman et al.
Researchers at the University of Cincinnati School of Medicine and Cincinnati Children’s Hospital have discovered a new method to increase both the speed and success rates of drug discovery.
The study, published August 30 in the journal Scientific progressoffers new promise in the discovery of new drugs.
“We hope to accelerate the drug discovery timeline from years to months,” said Alex Thorman, Ph.D., co-first author and a postdoctoral researcher in the Department of Environmental and Public Health Sciences in the School 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. Then, they 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 sped up the work time from months to minutes, reducing the weeks of work required for the initial screening to an afternoon.
Thorman said this method of faster screening of compounds that could become drugs speeds up the drug discovery process. But it’s not just speed that’s crucial.
He added that this new approach is more effective in identifying potentially effective compounds.
“And the accuracy will only improve, hopefully providing new hope to many people with diseases with no known cure, including those with cancer,” Thorman said.
It can also create more targeted treatment options in precision medicine, an innovative approach to tailoring disease prevention and treatment by taking into account differences in individuals’ genes, environments and lifestyles.
“An accelerated drug discovery process could also be a game changer in terms of our ability to respond to public health crises, such as the COVID-19 pandemic,” Thorman said. “The timeline for developing effective drugs could be accelerated.”
More information:
Alexander Thorman et al., Accelerating drug discovery and repurposing by combining transcriptional signature connectivity with docking, Scientific progress (2024). DOI: 10.1126/sciadv.adj3010. www.science.org/doi/10.1126/sciadv.adj3010
Provided by the University of Cincinnati
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