RESEARCH MONOGRAPH · KDC-MN-302

SRT1720

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

56/100

The cleaner research-tool STAC that survived the assay-artifact controversy, useful in vitro but never moved to humans

SRT1720 is the earlier Sirtris SIRT1 activator that became the workhorse research tool for studying STAC-mediated SIRT1 activation in animal models. It pre-dates SRT2104 and never had a clinical development program, so it lives entirely in the preclinical literature as a tool compound. The good news is that the preclinical literature is genuinely substantial, particularly the metabolic and lifespan work from the Auwerx lab in mice.

The mechanism story is the same controversy that hit all the STACs. SRT1720 was originally identified using the SIRT1 activity assay with a fluorogenic peptide substrate, the assay was later shown to produce artifactual activation signals with the fluorophore-conjugated substrates, and the literature went through a corrective phase where the substrate-specific activation profile got more carefully characterized. The current view is that SRT1720 does allosterically activate SIRT1 against natural acetylated substrates but the activation is partial and substrate-dependent, not the unconstrained activator the original assay suggested.

The in vivo metabolic work survived the controversy. Mitchell et al (2014) at the NIA showed lifespan extension in obese mice and metabolic improvements in standard chow-fed mice with chronic SRT1720 administration. The Auwerx group has multiple papers on SRT1720 improving mitochondrial function and metabolic flexibility in mouse models. So whatever the SIRT1 activation mechanism actually is, something useful is happening in the in vivo work.

What we like: substantial preclinical literature, well-characterized pharmacology in mice, and a useful research tool for any SIRT1-dependent pathway work. The Auwerx and Sinclair papers give you a reasonable methodological reference.

What we dont love is the lack of human data. SRT1720 never went into humans, and the SRT2104 clinical experience (which is the closest analog) was modest at best. So the translational confidence on SRT1720 specifically is genuinely low.

Sourcing for SRT1720 is research-only material. The molecule is reliably available from competent research-chemical suppliers, HPLC purity above 98 percent is standard, and the stability is fine for typical research use.

For SIRT1 pathway research in mice, SRT1720 is a defensible tool. For predicting anything about human SIRT1 activation, the field has shifted away from STACs toward NAD+ precursor work where the mechanism is more directly addressable.

Evidence: 50
Mechanism: 55
Reliability: 55
Safety: 70
Sourcing: 70
Value: 55
Signal: 50
Staying power: 45

Plain-language summary Intrigue 50 / 100

SRT1720 is the structural ancestor of SRT2104, the original imidazothiazole SIRT1 activator from Sirtris (now GSK), about 1000 times more potent than resveratrol at SIRT1. Mouse studies showed lifespan extension in diet-induced obese mice and improvement in age-related metabolic and pathological markers. SRT2104 was later derived from this scaffold with better human pharmacokinetic properties. Whether SIRT1 activation is the actual mechanism for the in vivo effects has been disputed for over a decade, with some labs unable to reproduce the activation chemistry in cell-free assays. Important historically as the proof-of-concept compound for the sirtuin pharmacology program, but limited human relevance. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Selective SIRT1 activator

An imidazothiazole SIRT1 activator; the structural lineage compound from which SRT2104 was developed.

Abstract

SRT1720 (CAS 925434-55-5; molecular formula C22H19N5OS2; molecular weight 433.55) is an imidazothiazole SIRT1 activator developed at Sirtris Pharmaceuticals as a potent (approximately 1000-fold over resveratrol) and selective sirtuin 1 activator. Mechanism is allosteric SIRT1 activation comparable to SRT2104. Mouse studies demonstrated lifespan extension in diet-induced obese mice, improved metabolic parameters, and reduced age-related pathology. The compound was the foundation for the broader Sirtris drug discovery program; SRT2104 was developed as a more drug-like successor with better human pharmacokinetics. SRT1720 is used preferentially in academic research where the established mouse pharmacology is valuable. Plasma half-life is approximately 8 to 10 hours.

Mechanism of action

Imidazothiazole SIRT1 allosteric activator; mechanism comparable to SRT2104 with greater potency than resveratrol.

Reported research dose ranges

Mouse studies 100 mg/kg; limited human data.

References

Milne JC, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007.
Minor RK, et al. SRT1720 improves survival and healthspan of obese mice. Sci Rep 2011.
Mitchell SJ, et al. The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Rep 2014.

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KDC-MN-302

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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SRT1720

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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