SR9009 Benefits: What Studies Report

SR9009, also referred to as stenabolic, appears in the published literature as a synthetic agonist of the REV-ERB nuclear receptors, a description used by researchers in a 2026 liver cancer study that tested the compound alongside sorafenib (PMID 41554703). REV-ERBα (NR1D1) and REV-ERBβ (NR1D2) are transcriptional repressors embedded in the circadian clock machinery, and the therapeutic interest in SR9009 comes from that position: a drug that engages the clock may, in principle, touch metabolism, immunity, sleep and cell growth at once.

This page organises what published studies actually measured and reported, grouped by outcome domain, with the model system labelled in each case. It does not describe benefits as established outcomes in humans. Where a frequently repeated claim has no support in the papers reviewed here, that is stated plainly. This page is for educational purposes only and is not medical advice; consult a licensed physician before considering anything related to your health.

How to read this evidence

Three distinctions matter more than any single result. First, species and system: a result in cultured cells is a mechanistic observation, not a physiological one. Second, compound identity: several papers in this area study REV-ERB biology using genetic models or different agonists rather than SR9009 itself, such as a 2026 report on the REV-ERB agonist STL1267 in a TGFβ1-driven human lung fibroblast model (PMID 41512274). Third, target specificity: researchers reported that SR9009 inhibited lethal prostate cancer subtype 1 by regulating the LXRα/FOXM1 pathway independently of REV-ERBs, which complicates the assumption that every SR9009 effect is a REV-ERB effect (PMID 36357378).

Metabolic and liver outcomes

The metabolic domain is where the animal literature is most developed. In a mouse model of non-alcoholic steatohepatitis, researchers reported that REV-ERB agonism improved liver pathology (PMID 33002003). In a separate line of work, the study of hepatic gluconeogenesis reported that Rev-erbα activation down-regulated the hepatic Pck1 enzyme and lowered plasma glucose in mice (PMID 30639375).

These are mechanistically coherent findings: the clock repressor sits upstream of genes governing hepatic fuel handling, so pharmacological engagement shifted the measured markers. What they are not is evidence of a metabolic benefit in people. Both reports describe rodent endpoints measured in a controlled laboratory setting, and neither the mouse NASH study (PMID 33002003) nor the glucose study (PMID 30639375) involved human participants.

Drug-induced liver injury as a separate question

A 2025 expert review examined the regulation of cyclophosphamide-induced hepatotoxicity by REV-ERBα modifiers, placing the receptor in the context of how the liver handles chemotherapeutic insult rather than in the context of performance or body composition (PMID 40211567). That framing is a reminder that REV-ERB-directed compounds are studied in both directions — as potential protectors and as agents whose hepatic effects require characterisation.

Sleep and circadian outcomes

Because REV-ERBs are clock components, sleep is one of the more direct outcome domains. A 2016 study on pharmacological targeting of the REV-ERBs in sleep/wake regulation investigated whether REV-ERB ligands alter sleep architecture in an animal model (PMID 27603791). Readers sometimes encounter SR9009 described as a sleep aid or as a wakefulness agent; the published work frames it as a tool for probing sleep/wake regulation rather than as a treatment with a settled direction of effect in humans (PMID 27603791).

Related circadian work illustrates how consequential clock disruption can be. Researchers reported that disrupting the key circadian regulator CLOCK led to age-dependent cardiovascular disease (PMID 28223222). That study did not test SR9009, but it is part of the background rationale for why pharmacological clock modulation is studied at all — and why its long-term consequences are treated as an open question.

Inflammation and immune outcomes

Several papers examine REV-ERB and clock biology in immune contexts without using SR9009 as the probe. The study of decidual macrophages reported that circadian rhythm-associated Rev-erbα modulated macrophage polarization via the PI3K/Akt signalling pathway (PMID 33934423). A 2026 cell study reported that berberine alleviated an LPS-induced inflammatory response through targeted activation of NR1D1 in bovine endometrial epithelial cells — the same receptor SR9009 engages, but a different molecule and a bovine cell system (PMID 42150288).

The direction of clock–inflammation relationships is not uniform. In a 2025 report, genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduced colonic inflammation (PMID 40307620) — that is, removing a clock component lowered an inflammatory readout in that tissue. Anyone extrapolating from "clock drug equals less inflammation" has to account for findings like this one (PMID 40307620).

Oncology models

The largest cluster of SR9009-specific publications sits in cancer biology. A 2020 study reported that SR9009 induced a REV-ERB dependent anti-small-cell lung cancer effect through inhibition of autophagy (PMID 32292508). A 2022 study reported that SR9009 inhibited lethal prostate cancer subtype 1 by regulating the LXRα/FOXM1 pathway independently of REV-ERBs (PMID 36357378). A 2026 report described SR9009 as a REV-ERB agonist that potentiated sorafenib efficacy in liver cancer by targeting metabolic vulnerabilities (PMID 41554703).

Two observations follow. First, these are preclinical oncology investigations, not treatments available to patients. Second, the contrast between the REV-ERB dependent lung cancer effect (PMID 32292508) and the REV-ERB independent prostate cancer effect (PMID 36357378) is a live methodological issue: a compound with meaningful off-target activity cannot be used as a clean readout of receptor pharmacology, and its effects in one tissue do not predict another.

Fibrosis

Fibrosis has been probed with a related chemical tool rather than SR9009. A 2026 study reported that STL1267 inhibited myofibroblast differentiation in a TGFβ1-driven human lung fibroblast model (PMID 41512274). This is an in-vitro result with a different REV-ERB agonist, and it is listed here as adjacent evidence about the receptor class, not as an SR9009 finding (PMID 41512274).

Claims with little or no support in these papers

Several outcomes commonly attached to SR9009 are simply not represented in the literature summarised on this page:

• Endurance capacity and "exercise in a bottle" effects. None of the papers cited here measured running capacity, VO₂, or skeletal-muscle mitochondrial endpoints; the metabolic data in this set are hepatic, such as the Pck1 and plasma glucose findings in mice (PMID 30639375).
• Fat loss or body-composition change in humans. No human trial appears in this citation set; the closest metabolic pathology endpoint is liver histology in a mouse NASH model (PMID 33002003).
• Muscle growth. No paper here reported hypertrophy or strength outcomes.
• Human dosing, bioavailability or pharmacokinetics. The papers here are mechanistic and preclinical, including the sleep/wake pharmacology work (PMID 27603791), and this page therefore states no dose.

The absence of evidence in this set is not proof that an effect does not exist; it means the claim is not supported by the papers listed below.

Safety and Adverse Events: What Studies Report

The studies collected here were designed around efficacy and mechanism rather than human tolerability, so they do not constitute a safety profile. The most directly safety-adjacent paper examined how REV-ERBα modifiers regulate cyclophosphamide-induced hepatotoxicity, which situates the receptor within drug-induced liver injury biology (PMID 40211567). Evidence of off-target pharmacology — SR9009 acting through LXRα/FOXM1 independently of REV-ERBs — is also relevant to risk assessment, because off-target activity broadens the range of tissues a compound may affect (PMID 36357378). Finally, circadian disruption itself carries documented consequences in animals: researchers reported that disrupting CLOCK led to age-dependent cardiovascular disease (PMID 28223222).

Regulatory status

SR9009 is not an approved medicine. It appears in the literature as an investigational chemical tool used in preclinical research, including the cancer and metabolic models described above (PMID 41554703, PMID 33002003). Materials sold for laboratory work are typically labelled research-use-only, meaning they are not intended for human consumption.

Bottom line

Across the papers summarised here, SR9009 has been studied for — not shown to deliver — effects on liver pathology in a mouse NASH model (PMID 33002003), hepatic glucose handling in mice (PMID 30639375), sleep/wake regulation (PMID 27603791), and tumour cell behaviour in lung, prostate and liver cancer models (PMID 32292508, PMID 36357378, PMID 41554703). For a broader background on the molecule and its receptor targets, see the SR9009 overview.

References

• Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation (EMBO reports, 2025)
• SR9009 inhibits lethal prostate cancer subtype 1 by regulating the LXRα/FOXM1 pathway independently of REV-ERBs (Cell Death & Disease, 2022)
• SR9009 induces a REV-ERB dependent anti-small-cell lung cancer effect through inhibition of autophagy (Theranostics, 2020)
• Regulation of cyclophosphamide induced hepatotoxicity by REV-ERBα modifiers (Expert Opinion on Drug Metabolism & Toxicology, 2025)
• Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation (PLoS One, 2016)
• Circadian rhythm-associated Rev-erbα modulates polarization of decidual macrophage via the PI3K/Akt signaling pathway (American Journal of Reproductive Immunology, 2021)
• STL1267 inhibits myofibroblast differentiation in a TGFβ1-driven human lung fibroblast model (American Journal of Physiology. Cell Physiology, 2026)
• Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer (Cell Death Discovery, 2026)
• Berberine alleviates LPS-induced inflammatory response by targeted activation of NR1D1 in bovine endometrial epithelial cells (International Immunopharmacology, 2026)
• Disrupting the key circadian regulator CLOCK leads to age-dependent cardiovascular disease (Journal of Molecular and Cellular Cardiology, 2017)
• REV-ERB agonism improves liver pathology in a mouse model of NASH (PLoS One, 2020)
• Rev-erbα activation down-regulates hepatic Pck1 enzyme to lower plasma glucose in mice (Pharmacological Research, 2019)