SR-9011

updated

SR-9011 is an experimental REV-ERB agonist, a chemical probe that alters clock-gene signaling, related to but structurally distinct from SR9009. It is promoted for fat loss, endurance, better sleep and as a senolytic. Small mouse studies found higher oxygen consumption, lower fat mass and shifts in wake and sleep stages by time of day, but the larger endurance and obesity results often cited used SR9009, and the records hold no human administration study. Graded D for short mouse studies with no human efficacy or pharmacokinetic data; WADA prohibits it in sport at all times.

experimental REV-ERB agonist chemical probe

  • Also written SR9011 or SR 9011
  • Distinct from SR9009 despite shared REV-ERB research origin
  • No human trial or pharmacokinetic study in the cited records
  • WADA explicitly prohibits SR9011 in 2026

Is SR-9011 the same compound as SR9009?

No. SR-9011 and SR9009 are related synthetic REV-ERB probes from the same research program but have different chemical structures and PubChem records. A result that used only SR9009 cannot be relabeled as SR-9011 evidence.

source: PubChem · SR9011 identity, National Center for Biotechnology Information. PubChem CID 57394021.

source: Solt et al. · SR9011 discovery evidence, Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012. DOI 10.1038/nature11030.

How does it affect REV-ERB and immune cells?

SR-9011 increases REV-ERB repression in reporter systems and changes clock-gene expression. Its cellular effects extend beyond inflammatory markers.

In newborn-rat microglia, challenge-induced inflammatory signals fell and IL-10 increased. Phagocytosis, mitochondrial respiration and ATP-linked metabolism also fell, without a 24-hour viability loss. These mixed changes do not demonstrate net neuroprotection.

Direct weak LXR-alpha activity complicates selectivity. An often-cited REV-ERB double-knockout experiment tested SR9009; it raises a related-chemistry question but is not an exact SR-9011 knockout result.

source: Solt et al. · SR9011 discovery evidence

source: China-affiliated primary-microglia study, Wolff SEC, Wang XL, Jiao H, Sun J, Kalsbeek A, Yi CX, Gao Y. The Effect of Rev-erbα Agonist SR9011 on the Immune Response and Cell Metabolism of Microglia. Frontiers in immunology. 2020. DOI 10.3389/fimmu.2020.550145.

source: Trump et al. · LXR cross-activity, Trump RP, Bresciani S, Cooper AW, Tellam JP, Wojno J, Blaikley J, Orband-Miller LA, Kashatus JA, Boudjelal M, Dawson HC, Loudon A, Ray D, Grant D, Farrow SN, Willson TM, Tomkinson NC. Journal of Medicinal Chemistry. 2013;56:4729-4737. DOI 10.1021/jm400458q.

What did SR-9011 actually do in the metabolic studies?

The original paper did measure higher oxygen consumption and lower fat mass after SR-9011 in mice. Its longer obese-mouse glucose, lipid and body-composition experiment used SR9009.

Figure 3 tested injected SR-9011 for 10 to 12 days in groups of roughly six to ten mice. Oxygen consumption increased and fat mass fell despite lower activity; food-intake rate and respiratory exchange ratio were unchanged.

Figure 5 used SR9009 for the 30-day diet-induced-obesity experiment, while panel 5f separately reported SR-9011 lipids in lean mice. The separate endurance paper also used SR9009. None establishes oral-human exposure or performance.

source: Solt et al. · SR9011 discovery evidence

Is every SR-9011 effect proven to be REV-ERB-mediated?

No. The original broad nuclear-receptor reporter panel looked selective, but a later biochemical study found that SR-9011 could displace an LXR-alpha ligand and increase the LXR target ABCA1 in cells. Assay disagreement means 'specific REV-ERB agonist' is too absolute.

The primary-microglia study used SR9011 as a REV-ERB agonist but did not include independent target perturbation, so its cellular changes are not proof that each effect required REV-ERB. The compound-specific LXR assay remains a separate selectivity caution.

source: Solt et al. · SR9011 discovery evidence

source: Trump et al. · LXR cross-activity

source: China-affiliated primary-microglia study

Is there a human half-life, safe threshold, or interaction profile?

No. Human liver-microsome work identified candidate metabolites, and a retrospective anti-doping screen found no positive samples in the tested collection. Neither is human administration PK. No trial supplies a half-life, adverse-event denominator, contraindications, interactions, safe exposure, or monitoring guidance.

Microsomes are an in-vitro enzyme system. A doping sample with no detected SR-9011 does not show safety and does not prove nobody used the compound. Because the molecule changes clock and metabolic transcription in models, timing and drug-interaction claims require human data that the cited studies do not provide.

source: Human-liver-microsome metabolic study, Geldof L, Deventer K, Roels K, Tudela E, Van Eeno P. In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011. International journal of molecular sciences. 2016. DOI 10.3390/ijms17101676.

source: ClinicalTrials.gov · no SR-9011 study, ClinicalTrials.gov search of the intervention-name and brief-title fields for SR9011 and its spelling variants, run on 10 September 2026.

Is SR-9011 approved or permitted in tested sport?

No approved medicine or human clinical program appears in the cited records. WADA's 2026 S4.4.1 section explicitly names SR9011 among REV-ERB-alpha agonists prohibited at all times.

source: ClinicalTrials.gov · no SR-9011 study

source: WADA 2026 · SR9011 named, World Anti-Doping Agency. The 2026 Prohibited List, effective 1 January 2026.

Does it improve sleep or act as a senolytic?

SR-9011 altered mouse wake, NREM and REM measures according to circadian timing. It also affected selected cancer and oncogene-induced-senescent cells. Better human sleep and clinical senolysis remain unestablished.

Wakefulness is not the same outcome as restorative sleep. The injected-mouse sleep experiments cannot establish an insomnia treatment or a human circadian-reset schedule.

SR-9011 appears in the cancer and senescent-cell experiments, while the frequently cited glioblastoma survival and xenograft treatment experiments used SR9009. A 2025 glioblastoma cell study found limited SR-9011 monotherapy activity in T98G cells and stronger combination effects with temozolomide. Patient-derived models are not treated patients.

source: Sleep architecture and emotional behavior in mice, Banerjee S, Wang Y, Solt LA, Griffett K, Kazantzis M, Amador A, El-Gendy BM, Huitron-Resendiz S, Roberts AJ, Shin Y, Kamenecka TM, Burris TP. Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. Nature communications. 2014. DOI 10.1038/ncomms6759.

source: Sulli et al., cancer and oncogene-induced senescence, Sulli G, Rommel A, Wang X, Kolar MJ, Puca F, Saghatelian A, Plikus MV, Verma IM, Panda S. Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence. Nature. 2018. DOI 10.1038/nature25170.

source: Personalized glioblastoma chronotherapy, 2025, Personalized glioblastoma chronotherapy, 2025. https://www.nature.com/articles/s41698-025-01205-z

Studies and sources

PubChem · SR9011 identity

Official chemical identity record

National Center for Biotechnology Information. PubChem CID 57394021.

The record identifies SR9011 with formula C23H31ClN4O3S, molecular weight 479.0 g/mol, CAS 1379686-29-9, and UNII VYI79FLZ6W.

Study design
Chemical database record

Identity registration is not approval or product authentication.

Read the original source
Solt et al. · SR9011 discovery evidence

Primary preclinical study

Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012. DOI 10.1038/nature11030.

Figures 1 to 4 include direct SR9011 reporter, clock, gene and mouse experiments. Figure 3 uses 10 to 12-day injected SR9011 in small mouse groups (6 to 10) and reports higher oxygen consumption and lower fat mass despite lower activity; food-intake rate and respiratory exchange ratio were unchanged. Figure 5’s 30-day diet-induced-obesity glucose/lipid/body-composition program uses SR9009, while panel 5f reports SR9011 lipids in lean mice. The obese-mouse numbers cannot all be assigned to SR9011.

Participants / model
HEK293 cells, mouse suprachiasmatic-nucleus explants, fibroblasts, and male C57BL/6 mice
Treatment
SR9011 and SR9009 in compound-specific cell, tissue, and injected mouse experiments
Follow-up
Acute and short repeated preclinical experiments
Study design
Discovery pharmacology across assays and mouse models
Funding
Academic and grant-supported program
Read the original source
Sleep architecture and emotional behavior in mice

Primary preclinical study

Banerjee S, Wang Y, Solt LA, Griffett K, Kazantzis M, Amador A, El-Gendy BM, Huitron-Resendiz S, Roberts AJ, Shin Y, Kamenecka TM, Burris TP. Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. Nature communications. 2014. DOI 10.1038/ncomms6759.

Injected SR9011 altered EEG-defined wake, NREM and REM measures depending on circadian timing and changed anxiety-like behavior. They do not demonstrate better human sleep, a clinically validated circadian-reset strategy or sustained cognitive performance.

Participants / model
Mice
Treatment
SR9011 versus vehicle at defined zeitgeber times
Follow-up
Acute and short preclinical experiments
Study design
Controlled animal EEG and behavior study
Read the original source
Trump et al. · LXR cross-activity

Preclinical medicinal-chemistry and cell receptor-assay study

Trump RP, Bresciani S, Cooper AW, Tellam JP, Wojno J, Blaikley J, Orband-Miller LA, Kashatus JA, Boudjelal M, Dawson HC, Loudon A, Ray D, Grant D, Farrow SN, Willson TM, Tomkinson NC. Journal of Medicinal Chemistry. 2013;56:4729-4737. DOI 10.1021/jm400458q.

In biochemical and cell assays, SR9011 showed weak LXR-alpha ligand displacement and increased ABCA1 expression, creating a compound-specific selectivity caveat despite the original reporter-panel result.

Participants / model
Biochemical receptor and THP-1 cell systems
Treatment
REV-ERB probe series including SR9011
Study design
Probe optimization and receptor profiling

SR9011-specific LXR binding and ABCA1 evidence were separated from SR9009-specific findings. Cell or binding cross-activity does not define a human interaction magnitude or exposure threshold.

Read the original source
Human-liver-microsome metabolic study

Analytical identity or detection study

Geldof L, Deventer K, Roels K, Tudela E, Van Eeno P. In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011. International journal of molecular sciences. 2016. DOI 10.3390/ijms17101676.

Fourteen candidate SR9011 metabolites were identified in vitro. Retrospective screening of 1,511 doping samples found neither SR9011 nor SR9009 positives in that collection. Human microsomes and urine do not establish human oral pharmacokinetics or absence of real-world use.

Participants / model
Pooled human liver microsomes and stored doping-control urine samples
Treatment
In-vitro SR9011 incubation and analytical sample screening
Follow-up
In-vitro incubations and retrospective sample set
Study design
Metabolite-identification and analytical screening study
Funding
Anti-doping research program
Read the original source
WADA 2026 · SR9011 named

Official anti-doping standard

World Anti-Doping Agency. The 2026 Prohibited List, effective 1 January 2026.

Section S4.4.1 explicitly names SR9011 among REV-ERB-alpha agonists prohibited at all times.

Participants / model
Athletes subject to the World Anti-Doping Code
Follow-up
Calendar year 2026
Study design
Anti-doping prohibited list
Funding
World Anti-Doping Agency

Sport prohibition is separate from medical approval.

Read the original source
China-affiliated primary-microglia study

Primary preclinical study

Wolff SEC, Wang XL, Jiao H, Sun J, Kalsbeek A, Yi CX, Gao Y. The Effect of Rev-erbα Agonist SR9011 on the Immune Response and Cell Metabolism of Microglia. Frontiers in immunology. 2020. DOI 10.3389/fimmu.2020.550145.

Newborn rat microglia exposed to SR9011 showed disrupted clock expression, reduced challenge-induced inflammatory signals and increased IL-10. Bead phagocytosis, mitochondrial respiration and ATP-linked metabolism also fell without a 24-hour viability loss. These mixed effects cannot be summarized as a pure neuroprotective gain.

Participants / model
Primary microglia isolated from 1- to 3-day-old male Sprague-Dawley rat pups
Treatment
Five micromolar SR9011 after dexamethasone synchronization, with immune and metabolic challenges
Follow-up
Cell experiments through 24 hours with time-course sampling
Study design
Controlled primary-cell circadian, immune, phagocytosis, and respirometry study
Funding
Chinese and Dutch academic funding listed in the paper; authors declared no commercial or financial conflict
Read the original source
Sulli et al., cancer and oncogene-induced senescence

Primary preclinical study

Sulli G, Rommel A, Wang X, Kolar MJ, Puca F, Saghatelian A, Plikus MV, Verma IM, Panda S. Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence. Nature. 2018. DOI 10.1038/nature25170.

SR9011 and SR9009 reduced viability and induced apoptosis in selected cancer and oncogene-induced-senescent cell experiments. SR9011 appears directly in the OIS/cancer cell figures; the reported glioblastoma mouse survival/xenograft treatment experiments use SR9009. Cell exposure around 20 micromolar over days is not a demonstrated achievable safe human exposure. “Senolytic” should specify the model and must not imply healthy lifespan extension.

Read the original source
Personalized glioblastoma chronotherapy, 2025

Primary preclinical study

Personalized glioblastoma chronotherapy, 2025. https://www.nature.com/articles/s41698-025-01205-z

Cell-line experiments compared timed temozolomide, KL001, SR9011 and combinations. In T98G cells, SR9011 alone had limited efficacy; temozolomide combinations were more effective, with results varying by model/timing. Patient relevance and PK-PD modeling do not mean patients received SR9011. This is a preclinical combination/chronotherapy result.

Read the original source

Why is SR-9011 in D tier?

D reflects short mouse studies of metabolic and sleep effects with no human efficacy or pharmacokinetic study. SR9009-only endurance, obesity and tumor-survival results do not belong to SR-9011.

how tiers are graded: methodology · every cited source · about reptides.

Research reference, not medical advice. Entries distinguish product labels, study doses and reported protocols. Check the linked source for the product, route and population.