SRT2104
SRT2104, small-molecule SIRT1 activator
Written by Aaron CuhaReviewed Sep 2026
Also known as: SIRT1 activator, STAC
The sirtuin-activating drug that actually reached randomised human trials, built to succeed where resveratrol's potency failed. Its human results were modest and it did not advance.
Overview
Sirtuins were the biggest idea in longevity biology in the 2000s, and resveratrol was supposed to be the drug. When resveratrol turned out to be too weak and too poorly absorbed, the response was to build purpose-designed sirtuin-activating compounds that were orders of magnitude more potent. SRT2104 was the one that got furthest.
It reached randomised human trials, including one in otherwise healthy smokers measuring cardiovascular and inflammatory endpoints, which is more than most compounds in this field manage.
The results were modest, the programme did not advance to approval, and the sirtuin activation hypothesis lost most of its momentum, partly on separate technical arguments about whether these compounds activate SIRT1 directly or only appear to in assays using a fluorescent substrate.
The page exists because the arc is instructive: a dominant mechanism, a purpose-built potent drug, real human trials, and no product.
Mechanism of action
Designed as a sirtuin-activating compound targeting SIRT1, an NAD-dependent protein deacetylase. SIRT1 deacetylates targets including PGC-1alpha, FOXO transcription factors and p53, and it was proposed as a mediator of dietary restriction benefits. The mechanistic controversy matters here: several sirtuin-activating compounds were shown to activate SIRT1 only in the presence of a fluorophore-tagged substrate, raising the question of whether the activation is an assay artefact rather than a property of the enzyme with its natural substrates. That dispute is unresolved and it shaped how these results were received.
Human evidence
Several early-phase randomised trials across different populations, with modest results, and no programme advancing to approval.
- A randomised trial in otherwise healthy smokers examined cardiovascular and inflammatory endpoints.
- The compound was studied in other early-phase settings including metabolic and inflammatory conditions.
- No result led to a phase 3 programme or an approval.
- The underlying mechanism is contested: the fluorophore-dependent activation problem raised the possibility that measured SIRT1 activation was an assay artefact.
- No human trial examined lifespan or healthspan.
What this does not tell you: Early-phase trials in specific populations with surrogate endpoints. The absence of advancement is informative but is not a published negative result, so it should not be read as a demonstrated failure in the way the RTB101 phase 3 can be. The mechanistic dispute means it is not even settled whether these compounds did what they were named for.
Reading the research record
The sirtuin arc is the best-documented example on this site of a dominant mechanism producing no drug. In the 2000s sirtuin activation was the leading explanation for why dietary restriction extends life, resveratrol was the popular embodiment of it, and a pharmaceutical programme was built to do properly what resveratrol did weakly. Purpose-designed compounds reached randomised human trials, the results were modest, nothing was approved, and a technical argument emerged that the compounds may have activated SIRT1 only in assays using a modified substrate.
Nothing about that arc says sirtuins are unimportant in biology. It says the path from an important enzyme to a useful drug is long, and that the strength of a mechanism's reputation is not evidence. That is worth remembering for every NAD precursor currently sold on a sirtuin rationale, since NAD is the cofactor these enzymes require.
The evidence, charted
Fig. 1 · evidence composition
1of 1 citation (100%) is in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Every citation here was published in 2013.
Too few distinct publication years on this page to plot as a timeline. The newest citation on file is from 2013, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2013
Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers
A randomised trial in otherwise healthy cigarette smokers examining cardiovascular effects of a purpose-designed SIRT1 activator. This is among the few randomised human trials of a sirtuin-activating compound, and the compound did not go on to approval.
Journal of the American Heart Association
Frequently asked questions
Do sirtuin activators work?
No sirtuin-activating compound has been approved for anything, and the purpose-built ones that reached randomised human trials produced modest results and did not advance. There is also an unresolved argument that their measured activation of SIRT1 depended on a modified assay substrate rather than reflecting real enzyme activation.
How does this relate to resveratrol or NAD supplements?
Directly. Resveratrol's longevity reputation came from sirtuin activation, and SRT2104 was built to do the same thing far more potently because resveratrol was too weak and poorly absorbed. NAD precursors are sold partly on the same rationale, since NAD is the cofactor sirtuins require. The failure of the potent purpose-built version is relevant context for all of them.
Can I get SRT2104?
No. It was never approved and is not available.