Trial reportBritish journal of clinical pharmacology2013
Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled, Phase I Clinical Study to Assess the Pharmacokinetics, Safety and Tolerability of SRT2104 Administered as Single and Multiple Doses in the Fed State to Normal Healthy Male Volunteers
Gender vs. Fed/Fasted State vs. Capsule/Liquid Suspension Formulation Study
Who cites it
77 citing papers in PubMed, 124 citations in OpenAlex.
- Assessing Colonic Exposure, Safety, and Clinical Activity of SRT2104, a Novel Oral SIRT1 Activator, in Patients with Mild to Moderate Ulcerative Colitis.Inflammatory bowel diseases · 2016Trial
- A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis.PloS one · 2015Trial
- A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.British journal of clinical pharmacology · 2014Trial
- Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers.Journal of the American Heart Association · 2013Trial
- A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers.PloS one · 2012Trial
- Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy.iScience · 2026Review
- SIRT1 activation by SRT2104 enhances mitophagy and reduces senescence in auditory cells.Scientific reports · 2026Article
- Novel applications of SIRT1 in Chronic Kidney Disease.Frontiers in medicine · 2026Review
- The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies.Journal of clinical and translational hepatology · 2025Review
- Review
- SIRT1-Mediated Mitochondrial Homeostasis in Cardiac Aging: Molecular Mechanisms and Therapeutic Implications.Aging and disease · 2025Review
- Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- The SIRT1 activator SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery.Cell death & disease · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Exploring Sirtuins: New Frontiers in Managing Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Senescent Astrocytes Derived from Human Pluripotent Stem Cells Reveal Age-Related Changes and Implications for Neurodegeneration.Aging and disease · 2024Article
- Current Trends in Sirtuin Activator and Inhibitor Development.Molecules (Basel, Switzerland) · 2024Review
- Emerging roles of SIRT1 activator, SRT2104, in disease treatment.Scientific reports · 2024Review
- SIRT1, resveratrol and aging.Frontiers in genetics · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimSRT2104 is a novel, first-in-class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated with oral dosing to aid in dose selection for subsequent clinical trials.
methodsIn the first-in-human study, there was both a single dose phase and 7 day repeat dose phase. Doses used ranged from 0.03 to 3.0 g. A radioactive microtracer study was subsequently conducted to determine systemic clearance, bioavailability and preliminary metabolism, and a crossover study was conducted to determine the effect of gender, formulation and feeding state on SRT2104 pharmacokinetics.
resultsSRT2104 was well tolerated in all of these studies, with no serious adverse reactions observed. SRT2104 displayed a dose-dependent, but sub-proportional increase in exposure following single dose and repeated dose administration. Accumulation of three-fold or less occurs after 7 days of repeat dosing. The mean bioavailability was circa 14% and the mean clearance was circa 400 ml min(-1). Although there were no substantial effects on exposure resulting from gender or formulation differences, a notable food effect was observed, manifested as up to four-fold increase in exposure parameters.
conclusionsIn the absence of an optimized formulation of SRT2104, the food effect can be used to maximize exposure in future clinical studies. Combined with the good tolerability of all doses demonstrated in these studies, the favourable selectivity profile of SRT2104 allows for the use of this SIRT1 modulator for target validation in the clinic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.