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Endocrine/metabolic disease


Sirtuin 1 (SIRT1)

In vitro and mouse studies suggest inhibiting SIRT1 specifically in neurons could help treat type 2 diabetes. Prior studies have suggested that peripheral SIRT1 activation could help treat the disease, but results have been inconsistent. In mice, neuron-specific knockout of Sirt1 increased insulin sensitivity and glucose tolerance compared with no knockout. Next steps could include identifying strategies to prevent peripherally acting SIRT1 activators from accessing the CNS.
Elixir Pharmaceuticals Inc.'s EX-527, an oral SIRT1 inhibitor, is in Phase II testing to treat Huntington's disease (HD).
GlaxoSmithKline plc's GSK2245840 SIRT1 activator is in Phase II testing to treat psoriasis. The compound completed Phase I/II trials for type 2 diabetes, but the pharma said it is no longer pursuing that indication with the compound.
Ildong Pharmaceutical Co. Ltd.'s SIRT1 activator, ID2244, is in preclinical development to treat metabolic syndrome.

SciBX 6(12); doi:10.1038/scibx.2013.288
Published online March 28, 2013

Findings unpatented; available for partnerships

Lu, M. et al. J. Biol. Chem.; published online March 1, 2013;
Contact: Jerrold M. Olefsky, University of California, San Diego, La Jolla, Calif.