SR9009 Side Effects: What Studies Report

What this page covers

SR9009 (also written SR-9009, and marketed in grey channels under the name "Stenabolic") is a synthetic small-molecule agonist of the REV-ERB nuclear receptors, a pair of circadian clock proteins that repress transcription of metabolic and inflammatory genes. It is not an approved medicine in any major jurisdiction, and the material circulating outside research settings is sold on a research-use-only basis.

The question of "side effects" assumes a body of safety data that, for this compound, does not exist in the usual form. In an approved drug's label, adverse events are listed with incidence percentages drawn from controlled trials in defined populations. For SR9009, the published record is preclinical: rodent disease models, cultured cells, isolated immune cells, one veterinary application and analytical work on drug metabolism. Studies in that record were designed to test efficacy hypotheses, not to enumerate harms. Where effects relevant to tolerability were reported, they usually appeared as mechanistic findings rather than as safety endpoints.

Everything below describes what researchers observed in those models. None of it constitutes a side-effect profile for humans, and none of it is a verdict on tolerability.

The shape of the evidence base

Among the published work summarised here, the study designs were: cardiac pressure-overload and myocardial infarction models in mice (PMID 35911512, PMID 29232411), hepatic drug-interaction and liver cancer work (PMID 40211567, PMID 41554703), murine glucose metabolism (PMID 30639375), immune and reproductive immunology models (PMID 34399700, PMID 33934423), and in vitro metabolism with doping-control detection in horses (PMID 34224639). No study in this set reported adverse-event frequencies, withdrawal rates, or laboratory-abnormality tables in human participants.

Cardiovascular findings: What Studies Report

Two cardiac studies in the verified set reported benefit rather than harm, but one of them raised an interpretive problem that bears directly on safety reasoning. A 2022 report in Frontiers in Cardiovascular Medicine found that SR9009 improved heart function after pressure overload independently of cardiac REV-ERB (PMID 35911512). Researchers described the cardiac effect as occurring without the intended receptor in the heart being required, which means at least part of the compound's activity in that model was not attributable to REV-ERB engagement.

That matters for adverse-event reasoning because off-target activity is, by definition, uncharacterised activity: a compound whose benefit in one tissue does not depend on its named target may also produce effects elsewhere that no target-based model predicts. The study did not catalogue such effects; it established only that the cardiac response was REV-ERB-independent (PMID 35911512).

Separately, a 2017 study reported that a Rev-erb agonist improved adverse cardiac remodeling and survival after myocardial infarction through an anti-inflammatory mechanism in mice (PMID 29232411). The study reported survival and remodeling outcomes in an injury model; it did not report cardiovascular adverse events in healthy animals, and no blood-pressure or arrhythmia safety data for SR9009 appear in the verified set.

Liver and drug-interaction findings: What Studies Report

The liver appears in the literature in two distinct ways. A 2025 analysis in Expert Opinion on Drug Metabolism & Toxicology examined the regulation of cyclophosphamide-induced hepatotoxicity by REV-ERBα modifiers (PMID 40211567). Researchers framed REV-ERBα modulation as something that changes how a hepatotoxic drug behaves in the liver — a pharmacological interaction signal rather than a report of SR9009 causing liver injury on its own.

A 2026 paper in Cell Death Discovery reported that the REV-ERB agonist SR9009 potentiated sorafenib efficacy in liver cancer by targeting metabolic vulnerabilities (PMID 41554703). Potentiation of another drug's effect is pharmacodynamically the same phenomenon that, outside a tumour, would be described as an interaction. Neither paper provided liver-enzyme safety data, histopathology scoring for SR9009 alone, or any human hepatic outcome (PMID 40211567).

Metabolic and glucose findings: What Studies Report

A 2019 study in Pharmacological Research reported that Rev-erbα activation down-regulated the hepatic gluconeogenic enzyme Pck1 and lowered plasma glucose in mice (PMID 30639375). The researchers presented the glucose reduction as a desired metabolic effect in that model. A glucose-lowering mechanism acting on hepatic gluconeogenesis is also the mechanism through which hypoglycaemia occurs, but the study did not report hypoglycaemic episodes, glucose nadirs in fasted or insulin-treated animals, or any threshold at which the effect became undesirable (PMID 30639375).

Circadian-metabolic coupling is relevant context here: a 2020 study reported that proinflammatory cytokines perturbed mouse and human pancreatic islet circadian rhythmicity and induced uncoordinated β-cell clock gene expression via nitric oxide, lysine deacetylases and immunoproteasomal activity (PMID 33374803). That study examined cytokines rather than SR9009, and it is cited here only to show that β-cell clock machinery is itself pharmacologically perturbable — not as evidence of any SR9009 effect on islets.

Immune and inflammatory findings: What Studies Report

Several papers reported immunosuppressive or immunomodulatory activity. A 2021 study in BMC Immunology reported that pharmacological activation of Rev-erbα suppressed LPS-induced macrophage M1 polarization and prevented pregnancy loss in a murine model (PMID 34399700). A 2026 veterinary paper reported that REV-ERB agonists modulated TH17 cell activity, framed as a path toward treatments for canine meningoencephalitis of unknown origin (PMID 42488849). A 2023 paper in Frontiers in Pharmacology reported REV-ERB activation as a pharmacological approach for inflammatory pain (PMID 37153791).

In each case, dampened inflammatory signalling was the intended outcome. Published immunology does not distinguish, at the receptor level, between "anti-inflammatory benefit" and "reduced immune responsiveness"; these are the same pharmacology described from different endpoints. None of these studies reported infection rates, immune-competence challenge testing, or any measure of whether suppressed macrophage or TH17 activity impaired host defence (PMID 34399700, PMID 42488849).

Reproductive and pregnancy findings: What Studies Report

Two papers touched reproductive tissue. A 2021 study in the American Journal of Reproductive Immunology reported that circadian rhythm-associated Rev-erbα modulated polarization of decidual macrophages via the PI3K/Akt signalling pathway (PMID 33934423), and the murine study described above reported prevention of pregnancy loss following Rev-erbα activation in an LPS-challenge model (PMID 34399700).

These are mechanistic findings in inflammation-driven pregnancy models. The verified literature contains no reproductive toxicology study of SR9009 — no fertility, embryo-fetal development, teratogenicity or lactation data — and the presence of receptor activity in decidual tissue is a reason such studies would be informative, not a substitute for them (PMID 33934423).

Cytotoxicity findings: What Studies Report

A 2018 paper in Nature reported that pharmacological activation of REV-ERBs was lethal in cancer cells and in oncogene-induced senescence (PMID 29320480). Cell death was the reported therapeutic endpoint there, and the same mechanism was later invoked in the liver cancer combination work reporting potentiation of sorafenib (PMID 41554703).

From a toxicology standpoint, a compound class whose principal reported anticancer action is induction of cell death is one whose effects on normal proliferating tissues warrant characterisation. The Nature study's scope was lethality in transformed and senescent cells; it did not provide an adverse-event frequency table or a human tolerability dataset (PMID 29320480).

Metabolism, detection and analytical context

A 2022 paper in Drug Testing and Analysis reported the in vitro metabolism of SR-9009 and the subsequent detection of its metabolites in routine equine plasma and urine doping control samples (PMID 34224639). That work was analytical — identifying metabolite markers for anti-doping screening — and it documents that the compound has been encountered in doping-control contexts. It did not assess toxicity, and it does not describe human pharmacokinetics.

What is not reported

Stating gaps plainly is more useful than inferring around them. Across the verified literature summarised on this page, the following do not appear:

• Controlled human trials of SR9009 with any adverse-event reporting; the cardiac, hepatic and metabolic findings cited are animal and cell work (PMID 35911512, PMID 30639375).
• Incidence rates, severity grading or dose-limiting toxicity thresholds for any organ system.
• Long-term or repeat-dose toxicology, carcinogenicity or genotoxicity data.
• Human pharmacokinetic data; the available metabolism work was in vitro with equine sample detection (PMID 34224639).
• Systematic drug-interaction studies, although interaction-relevant pharmacology was reported with cyclophosphamide and sorafenib (PMID 40211567, PMID 41554703).
• Reproductive or developmental toxicology, despite reported activity in decidual immune cells (PMID 33934423).

How preclinical findings differ from a side-effect profile

Three distinctions explain why the sections above cannot be converted into a list of expected side effects. First, species: effects reported in mice and in canine immune cells (PMID 42488849) do not transfer directly to humans. Second, model state: most studies used diseased or challenged animals — pressure overload, infarction, LPS challenge, tumour-bearing — so the reported outcomes describe a drug acting on pathology, not on a healthy organism (PMID 29232411). Third, endpoint design: efficacy studies measure what they set out to improve, so an effect only becomes an "adverse event" when a study is built to look for it, and none of these were.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any health decision or any compound discussed here. SR9009 is not an approved therapeutic product, and nothing above should be read as a tolerability assessment.

References

• SR9009 improves heart function after pressure overload independent of cardiac REV-ERB (Frontiers in Cardiovascular Medicine, 2022)
• Regulation of cyclophosphamide induced hepatotoxicity by REV-ERBα modifiers (Expert Opinion on Drug Metabolism & Toxicology, 2025)
• Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer (Cell Death Discovery, 2026)
• Circadian rhythm-associated Rev-erbα modulates polarization of decidual macrophage via the PI3K/Akt signaling pathway (American Journal of Reproductive Immunology, 2021)
• REV-ERB activation as a novel pharmacological approach for treating inflammatory pain (Frontiers in Pharmacology, 2023)
• Rev-erbα activation down-regulates hepatic Pck1 enzyme to lower plasma glucose in mice (Pharmacological Research, 2019)
• Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism (PLoS One, 2017)
• Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence (Nature, 2018)
• Pharmacological activation of rev-erbα suppresses LPS-induced macrophage M1 polarization and prevents pregnancy loss (BMC Immunology, 2021)
• Modulation of TH17 cell activity by REV-ERB agonists: path toward novel treatments for canine meningoencephalitis of unknown origin (npj Veterinary Sciences, 2026)
• Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity (International Journal of Molecular Sciences, 2020)
• In vitro metabolism of the REV-ERB agonist SR-9009 and subsequent detection of metabolites in associated routine equine plasma and urine doping control samples (Drug Testing and Analysis, 2022)