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Scripps Research scientists identify first synthetic activator of 2 critical proteins
Date:11/19/2010

JUPITER, FL, November 19, 2010 Scientists from the Florida campus of The Scripps Research Institute have identified a novel synthetic activator of a pair of proteins that belong to a protein family playing key roles in human metabolism and immune function. The discovery could provide new and potentially more effective therapeutic approaches to diseases ranging from diabetes to osteoporosis.

The study was published in the November issue (Volume 5, Issue 11) of the journal ACS Chemical Biology.

"This new compound is particularly important because it works in vivo, and it is selective for certain receptors," said Tom Burris, a professor in the Department of Molecular Therapeutics at Scripps Florida who led the study. "These two properties give it significant potential as a possible therapeutic compound."

The new discovery represents the very first synthetic ligand (binding partner) that functions as an agonist (activator) of retinoid-related orphan (ROR) nuclear receptor. Nuclear receptors are protein molecules that mediate hormone activity inside the cell; they have been implicated in the progress of a number of cancers, and have also become drug development targets for diseases including type 2 diabetes, atherosclerosis, and metabolic syndrome.

Although scientists don't know the full therapeutic significance of the new synthetic ligand, its potential usefulness is clear, Burris noted.

"For example, loss of RORα in animal models renders them resistant to weight gain," he said, "while RORγ has been shown to be involved in development of cells that are implicated in autoimmune diseases and loss of RORγ results in animals that are resistant to these types of disease."

RORα has also been shown to be required for normal bone development; animal models lacking this receptor develop osteoporosis, strongly suggesting that RORα agonists may have potential as a treatment of this disea
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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