ARTICLE | Clinical News

GlaxoSmithKline preclinical data

August 23, 2010 7:00 AM UTC

Researchers at GlaxoSmithKline's Sirtris Pharmaceuticals Inc. subsidiary reported kinetic and biophysical data for 26 of its sirtuin 1 ( SIRT1)-activating compounds - including SRT1460, SRT1720 and SRT2183 - suggesting that the compounds interact directly with SIRT1 and activate SIRT1-catalyzed deacetylation through an allosteric mechanism without the need for a fluorophore tag on the substrate. Data were published in the Journal of Biological Chemistry.

The researchers said the data are "at odds with" findings from a previous study published in JBC by researchers at Pfizer Inc. (NSYE:PFE, New York, N.Y.) suggesting that Sirtris' then lead SIRT1-activating compound, SRT501, and SRT1460, SRT1720 and SRT2183, appeared to activate SIRT1 only when linked to a fluorophore, and that the compounds exhibited multiple off-target activities against receptors, enzymes, transporters and ion channels. ...