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Scripps Florida Team Awarded $1.8 Million Grant to Develop Drugs for Heart Disease and Rheumatoid Arthritis

JUPITER, FL – January 24, 2017 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded approximately $1.8 million from the National Institute of General Medical Sciences of the National Institutes of Health to develop a series of drug candidates for a number of diseases, including heart disease, rheumatoid arthritis and several neurodegenerative disorders.

The co-principal investigators of the three-year project are TSRI Professor William R. Roush and Associate Professor Derek Duckett.

“This is an exciting project, and I think our combined efforts are well-positioned to make significant progress over the next three years,” said Roush.

The new project will focus on an enzyme known as ASK1, which is involved in mediating cell survival and programmed cell death, or apoptosis. ASK1 is part of a larger family of mitogen-activated protein kinases (MAP kinases), enzymes that help control a cell’s response to stress. A number of studies have shown that animal models lacking ASK1 have decreases in the size of myocardial infarctions (heart attacks) and a marked resistance to heart cell death.

“ASK1 has been highlighted as a therapeutic target in several stress-related diseases and we expect that inhibitors of its activity will provide significant benefit in multiple disease states,” Duckett said.

Under a previous grant, Duckett and his colleagues completed a high throughput screening campaign aimed at identifying the best lead molecules to target ASK1, ultimately producing a series of small molecule inhibitor candidates from six different structural classes.

“This new grant is the result of another fruitful collaboration between Derek’s lab and mine,” Roush noted. “The starting point for our effort to develop a selective and brain penetrant ASK1 inhibitor originated from high throughput screening, molecular modelling for compound design, and initial rounds of synthesis and testing.”

The optimization strategy going forward, Duckett explained, will focus on developing inhibitor properties sufficient for use in pre-clinical testing, and ultimately, in safety assessment and clinical trials.

The number of the grant is 1R01GM122109-01.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.

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TSRI Professor William R. Roush (above) and Associate Professor Derek Duckett will lead the new project on the Florida campus of The Scripps Research Institute. (Photos by James McEntee.) (High-res image)


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