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Grant to fund development of drug candidates for rheumatoid arthritis, neurodegenerative disorders

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded approximately $1.2 million from the National Institute of General Medical Sciences of the National Institutes of Health to identify, test and develop a series of drug candidates for a number of diseases, including rheumatoid arthritis, heart disease and several neurodegenerative disorders.

Derek R. Duckett, associate scientific director in TSRI's Translational Research Institute, and Peter S. Hodder, senior director of lead identification at the Translational Research Institute, will act as co-principal investigators for the three-year grant.

The project will focus on an enzyme known as ASK1, which is part of a larger family of mitogen-activated protein kinases (MAP kinases) that help control how cells respond to stress and is involved in mediating cell survival and programmed cell death (apoptosis). Genetic target validation studies have demonstrated that loss of this kinase shows remarkable efficacy in animal models of various diseases.

"While ASK1 is a highly druggable target, no tool compounds are currently available to probe its biology," Duckett pointed out. "This award will help us remedy the situation."

The new grant will allow the Scripps Florida scientists to perform a high-throughput screening campaign of the TSRI compound collection at their state-of-the-art screening facility. "Our team approach will identify the best lead molecules that will help define the roles that ASK1 plays in normal physiological processes as well as in disease states," Duckett said. "Such leads will also serve as good starting material for chemistry optimization efforts for future therapeutics."

"A very exciting prospect of this research effort is that Scripps's drug discovery compound collection will be assayed for novel inhibitors of ASK1 activity," said Hodder. "Past screening efforts with this collection yielded the antecedents of clinically relevant compounds, and the research plan we have in place bodes well for a similar outcome from this effort."

Contact: Eric Sauter
Scripps Research Institute

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Grant to fund development of drug candidates for rheumatoid arthritis, neurodegenerative disorders
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