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SRT-2104 is designed to boost the production of one particular sirtuin enzyme, SRT1, which is believed to enhance metabolic function in cells and mimic the effects of a low-calorie diet. It is intended to be more specific in its action than resveratrol, which can have multiple biological effects, and it’s about 1,000 times as potent as the red-wine-derived compound. As Sirtris indicated last year, it has ended development of its proprietary formulation of resveratrol, SRT-501, for Type 2 diabetes, in favor of SRT-2104. In mouse studies, SRT-2104 reduced blood sugar levels and boosted the ability of the insulin to control blood sugar. The new clinical trial will provide an opportunity to see if such effects are reproducible in humans.
In addition to the diabetes work, Sirtris has done pre-clinical testing of its sirtuin-activator drugs on certain targets related to inflammation, such as TNF-alpha proteins. In mice, a compound known as SRT-2183 suppressed proteins that are overabundant in patients with inflammatory bowel disease. Still, Sirtris did not say whether it plans to pursue human clinical trials of an IBD treatment (although its preclinical work indicates that is a distinct possibility.)
Sirtris CEO Christoph Westphal said during the Harvard Medical School meeting that there are 15 active clinical trials of drugs that activate sirtuins, at his firm and others around the world, to treat a variety of diseases. “There are going to be a lot of people working on it,” he said. “It’s a huge field.”