SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1
clinical paper · 2010
LINK
SUMMARY
Pfizer laboratory paper showing that resveratrol and several Sirtris-developed synthetic sirtuin-activating compounds (STACs), including SRT1720, do not directly activate SIRT1 against native, unlabeled peptide substrates; the activation signal reported in earlier studies depended on a fluorophore-conjugated substrate used in the screening assay. DOI resolved via Crossref; title and full author list match. Peer-reviewed mechanistic refutation, published independently of Sirtris.
NOTES
The mechanistic disconfirmation at the center of the case’s vague/surrogate-mechanism stage: seven years after the original 2003 Nature paper proposed direct SIRT1 activation as resveratrol’s mode of action, this independent industry laboratory paper showed the effect was an artifact of the assay, not a real interaction with the enzyme’s native substrate.