SR-9009
Not medical advice. PepTutor summarizes fallible research and community signal for trained practitioners; some compounds are research-only, unapproved, controlled, jurisdiction-dependent, or labeled not for human consumption.
Non-hormonal endurance and cutting support for users who can solve the route and timing problem.
No human clinical trials exist — every effect and safety claim is extrapolated from rodent data; the compound's REV-ERB-independent mechanisms include mitochondrial stress effects whose safety at human doses is completely unknown.
Non-hormonal endurance and cutting support for users who can solve the route and timing problem. The best read is cautiously favorable but narrow: SR-9009 is interesting when sublingual or injectable exposure is realistic, training volume matters more than strength gain, and the user accepts that every efficacy claim is still preclinical plus community translation rather than human trial evidence.
Insomnia and circadian disruption are the most documented adverse effects — dose timing after 5 PM reliably worsens sleep. Headaches and mild nausea reported at higher doses. Long-term human safety is entirely unknown; high-dose animal studies have shown liver damage. The 2019 PNAS finding of REV-ERB-independent effects on cell viability adds an uncharacterized off-target layer.
Moderate value if using injectable or sublingual; poor value if using oral capsules — most of the compound is destroyed by first-pass metabolism before reaching systemic circulation. Injectable costs ~$30-80/vial at 30 mg/mL; oral liquid at 20 mg/mL runs ~$40-60 for a typical 8-week supply at 20-30 mg/day.
Highly variable by administration route. Injectable and sublingual users generally report meaningful endurance and fat-loss effects within 1-2 weeks. Oral capsule users report inconsistent results that likely reflect the bioavailability problem rather than inefficacy. The animal data (50% increase in running capacity) is compelling but may not translate to humans at achievable doses.
Do not stack with other circadian-modulating compounds (SLU-PP-332, other REV-ERB ligands) — redundant mechanism with no additive benefit and potential additive circadian disruption.
Intro
SR-9009, branded Stenabolic, is a synthetic REV-ErbA agonist developed by Professor Thomas Burris at the Scripps Research Institute and first described in a landmark 2012 Nature paper.
It activates REV-ErbAα and REV-ErbAβ — nuclear receptors that are core components of the circadian clock machinery — with IC50 values of 670 nM and 800 nM respectively. REV-ErbA proteins function as transcriptional repressors that suppress BMAL1 and CLOCK gene expression, the positive arm of the circadian feedback loop. Pharmacologically activating them does not "fix" or "optimize" the circadian rhythm in any simple sense; it shifts the metabolic state those proteins normally create during specific phases of the 24-hour cycle.
It is frequently misclassified as a SARM. This is wrong. SR-9009 has no androgen receptor activity, does not bind to AR, and does not suppress the HPG axis. The misclassification likely originated from its appearance in SARM marketing catalogs and its concurrent community adoption with LGD-4033 and Ostarine. The actual mechanism — circadian nuclear receptor modulation — is mechanistically closer to Cardarine (GW-501516, a PPARδ agonist) in its non-hormonal metabolic-modulation effects, though the two operate through entirely separate pathways with no receptor overlap.
The headline finding from Burris's 2013 Nature Medicine paper: mice with Rev-erbα activation via SR-9009 showed a 50% increase in running capacity measured by both time and distance. Treated mice developed an oxidative muscle fiber gene expression profile resembling trained athletes. Burris described it as animals that "get muscles like an athlete who has been training." This, combined with the fat-loss data in obese mice from the 2012 Nature paper, drove its rapid adoption in the bodybuilding and endurance community despite the complete absence of human trial data.
Community adoption peaked around 2014-2018. The compound's reputation bifurcated: users who found the oral powder largely ineffective (correctly attributing this to poor bioavailability), and a smaller group who switched to injectable or sublingual formats and reported results consistent with the animal data. That split persists today and explains the inconsistent community consensus. SR-9009 has been on the WADA prohibited list since 2009 — notably before robust community adoption — classified as a Hormone and Metabolic Modulator.
Observed Effects
Endurance and exercise capacity: The pivotal finding from Woldt et al. (Nature Medicine, 2013): SR-9009 treatment in mice increased running capacity by 50% measured by both time and distance.
Treated mice showed increased mitochondrial content in skeletal muscle and an oxidative-type gene expression profile. The mechanism proposed: REV-Erbα activation promotes both creation of new mitochondria and clearance of defective ones via autophagy regulation, net-increasing the functional mitochondrial pool. Community users taking injectable or sublingual SR-9009 consistently report endurance improvements, characterizing the effect as "engine efficiency" rather than stimulant-type energy — sustained aerobic capacity improvement rather than a rush. Oral users report inconsistent results, with many attributing null results to bioavailability failure.
Fat loss and metabolic effects: The 2012 Nature study (Solt et al.) demonstrated SR-9009 reduced fat mass in diet-induced obese mice while improving dyslipidemia and hyperglycemia. Downstream effects include decreased lipogenesis in white adipose tissue, increased fatty acid oxidation in skeletal muscle, reduced glucose storage, and increased basal oxygen consumption. A 2025 study (chronic low-dose, 10 mg/kg/day × 8 weeks) showed reduced weight gain and white fat mass in circadian-disrupted mice, with effects attributed to adipogenesis inhibition rather than energy expenditure changes. Community users report 1-2% body fat reduction over 8-week cycles when combined with caloric deficit and training; most acknowledge it is not a primary fat-loss tool on its own but a meaningful amplifier.
Anti-inflammatory and anxiolytic effects: REV-ErbA activation suppresses NLRP3 inflammasome activity and reduces IL-1β, IL-6, and MMP-9 expression in animal models. One mouse study demonstrated SR-9009 (injected twice daily for 3-10 days) reduced anxiety-like behavior with efficacy comparable to benzodiazepines. Community reports of reduced anxiety and improved sleep quality (when dosed early in the day) are consistent with this. The cardioprotective effects seen in the myocardial ischemia-reperfusion model (Reitz et al., 2019) suggest NLRP3 inflammasome suppression has tissue-level downstream consequences.
Important caveats: A 2019 PNAS paper (Dierickx et al.) demonstrated that SR-9009's effects on cell proliferation, metabolism, and gene expression are partially REV-ERB-independent — the compound affects hepatocytes and embryonic stem cells even when both REV-ERBα and REV-ERBβ are genetically deleted. The authors also showed SR-9009 causes mitochondrial stress in a REV-ERB-independent manner (decreased oxygen consumption rate, increased ATF4 — a mitochondrial stress marker). This means not all of SR-9009's effects are explained by the Rev-ErbA mechanism. Some may be off-target. None of this has been characterized in human safety studies.
Field Reports
What works: The most consistent community experience with SR-9009 is the endurance effect when exposure is timed correctly, especially before training with sublingual or injectable formats.
Users describe it as a "cleaner" endurance boost than stimulant pre-workouts — no crash, no heart rate spike, just the ability to sustain higher intensity for longer. This maps closely to the mitochondrial biogenesis mechanism.
Fat loss effects are real but secondary in community reports — most users describe it as an amplifier of existing dietary deficit rather than a primary fat-loss tool. Common phrasing: "it makes the cut feel effortless" rather than "it melted fat off."
Anxiety reduction is an underappreciated community finding. Multiple cycle logs document marked anxiety reduction — some users have described the effect as benzodiazepine-adjacent in quality without the sedation. The animal data supports this (benzodiazepine-comparable anxiolytic effect in mice). This effect appears more reliably than the fat-loss effect.
What doesn't work: Oral capsule dosing at 20-30 mg produces inconsistent results across users. The best explanation is product-quality variation interacting with individual first-pass metabolism differences — some batches reach low but meaningful systemic concentrations; others effectively deliver zero. Users who "try SR-9009 and feel nothing" are most likely experiencing bioavailability failure, not true non-response.
Common mistakes: (1) Dosing in the evening — the most frequent cause of reported insomnia. The compound promotes wakefulness in a circadian-dependent way; evening dosing reliably disrupts sleep. (2) Treating SR-9009 like a once-daily compound — the 4-6 hour half-life means a single morning dose provides no afternoon or evening coverage. (3) Not accounting for form — using oral capsules and expecting injectable-level results. (4) Expecting rapid strength gains — SR-9009 is not anabolic and doesn't produce weight-room performance improvements directly. The endurance benefit feeds into recovery and training volume, which eventually improves composition, but the mechanism is different from androgenic compounds.
Protocol refinements from experienced users: Morning + midday + pre-workout exposure is the standard pattern that experienced users describe. Pre-workout timing is specifically credited for in-session endurance improvement. Injectable users generally prefer subcutaneous over repeated IM use because the latter adds avoidable route burden.
Community Consensus
SR-9009 occupies a specific niche in the bodybuilding and endurance community: the "non-hormonal performance compound" that doesn't require bloodwork, doesn't suppress testosterone, and doesn't complicate a PCT.
That profile draws users who want performance enhancement without the overhead of a hormonal cycle — a category that has grown significantly as the SARMs market matured and PCT-avoidance became a priority for many.
The compound is most prevalent in two subgroups: competitive endurance athletes (cyclists, runners, OCR athletes) who value non-suppressive compounds and accept the WADA risk, and bodybuilders using it as a cutting cycle addition alongside SARMs or TRT. Its reputation in both groups is "real but unreliable" — the injectable and sublingual users are believers; the oral capsule users are often skeptics who abandoned the compound after two weeks of nothing.
The not-a-SARM framing is a persistent community education project. The research literature is clear that it is a Rev-ErbA agonist with no AR activity, yet catalog grouping and community habit kept it mentally associated with SARMs for years. This affects community understanding of its risks and mechanisms in ways that are sometimes beneficial (no PCT anxiety for oral SARM-takers who try SR-9009) and sometimes misleading (assumptions about liver toxicity drawn from C17-alkylated oral steroids).
The community never fully resolved the bioavailability debate — a small but vocal contingent argues that oral bioavailability is "good enough at 30 mg" and points to positive experiences. The larger practical consensus, developed through years of trial and error, is that sublingual or injectable formats produce reliably stronger results.
Risks & Monitoring
The adverse-effect picture for SR-9009 is unusually sparse in documented clinical evidence because no human trials exist. The profile that exists is almost entirely community-reported and animal-model extrapolation.
Circadian disruption and insomnia: SR-9009's most consistently reported adverse effect across community users is dose-timing-dependent sleep disruption. REV-ErbA modulates wakefulness during sleep phases in animal models — mice injected during daytime (their sleep phase) showed increased activity and decreased deep sleep. Applied to humans: doses taken after ~5 PM reliably produce a "wired" feeling that delays sleep onset. The effect is timing-dependent rather than dose-dependent — the same 10 mg dose causes insomnia if taken at 9 PM and has no sleep effect if taken at 9 AM. Mitigation: all doses before 5 PM. Some users paradoxically report improved sleep quality on morning-only dosing, possibly reflecting normalization of circadian gene expression rhythms.
Headaches and nausea: The second most commonly reported adverse effect. Reported more frequently at doses above 30 mg/day and in the first week of a cycle. Likely a CNS-level effect of REV-ErbA activation in the hypothalamus. Self-limits within 7-10 days in most reports; resolved by dose reduction.
Potential liver effects at high doses: High-dose SR-9009 administration in animal studies has produced liver damage (referenced in the 2025 chronic low-dose study as justification for using lower doses). No human hepatotoxicity cases are documented. SR-9009 is metabolized via human liver microsomes (8 identified metabolites in in vitro HLM assay). Whether community doses produce hepatic strain is unknown. Running LFTs at baseline and midcycle is reasonable if using for extended periods.
REV-ERB-independent off-target effects: The 2019 PNAS finding that SR-9009 decreases cell viability and causes mitochondrial stress via REV-ERB-independent pathways represents an unquantified risk. At 10 μM (test cell concentration), it reduced viability of both control and DKO cells. Whether this translates to any tissue effect at community doses in humans is unknown. Not a reason to classify the compound as acutely dangerous, but it is a reason to be honest that the mechanistic picture is incomplete.
No hormonal adverse effects: SR-9009 does not suppress testosterone, does not aromatize, and does not affect the HPG axis. No acne, no gyno, no suppression-driven fatigue, no fertility effects documented. No PCT required after standalone use.
For Women
Monitoring Panels
REQUIRED is a real safety gate. RECOMMENDED is the prudent default. OPTIONAL covers symptoms, risk factors, or tighter tracking.
SR-9009 is hepatically metabolized and high-dose animal data shows liver damage. Baseline establishes reference; midcycle check flags unexpected hepatic strain. Not required but reasonable for cycles over 8 weeks or doses above 30 mg/day.
Midcycle check at week 4-6 for extended cycles or doses above 30 mg/day. Discontinue if ALT/AST exceeds 3× ULN.
SR-9009 modulates lipid metabolism genes in the liver. Animal data shows reduction in plasma lipids. Baseline documents starting lipid health; midcycle data could show directional effects.
Animal data shows improved insulin sensitivity with SR-9009 treatment. Baseline glucose establishes reference for users interested in metabolic response tracking. Not a safety requirement.
Avoid With
Do not combine SR-9009 with the following. Sorted highest-severity first.
Why:Same receptor system — REV-ErbAα and REV-ErbAβ. Combined activation produces no additive biological benefit beyond what a single agonist achieves at full receptor occupancy, but doubles circadian disruption potential and off-target exposure.
What to do:SR-9011 is pharmacologically similar to SR-9009 with a slightly different metabolite profile. No reason to combine them.
Why:SR-9009's wakefulness-promoting effect via circadian receptor activity is additive with stimulant mechanisms. The combination substantially increases insomnia risk if any compound is taken in the evening. Keep all SR-9009 doses and stimulants before 3 PM for users sensitive to sleep disruption.
What to do:Not a pharmacokinetic interaction — both are active but in separate systems. Risk is purely additive circadian disruption.
Why:No interaction risk between SR-9009 and Cardarine — they operate on separate receptors (REV-ErbA vs. PPARδ). The note is about Cardarine's own toxicology: animal studies showed rapid multi-organ cancer development at high doses, which is why GlaxoSmithKline discontinued its clinical program in 2007. Cardarine is a WADA-banned carcinogen at high doses in animals. If stacking, this is the primary risk consideration — not from the SR-9009 side.
What to do:Cardarine is the most common SR-9009 stack partner. The combination itself has no interaction problem. Cardarine's own cancer finding should inform the decision to use it at all, independently of the stack.
Protocols By Goal
Fat loss / cutting: 20-30 mg/day sublingual in 3 doses (morning, midday, pre-workout) for 8-10 weeks.
Stack with Cardarine (10-20 mg/day, single AM dose) for synergistic fat-loss and endurance via complementary non-overlapping pathways (REV-ErbA + PPARδ). No hormonal interference. Cardarine's 24-hour half-life is administratively easier and balances SR-9009's demanding dosing schedule. Expect fat-loss contributions to appear at weeks 2-3; full effect develops by weeks 5-6. Combine with caloric deficit of 300-500 kcal/day. SR-9009 shifts the energy substrate toward fat oxidation — the metabolic environment does the rest.
Endurance enhancement: 20-25 mg/day sublingual or injectable in 2-3 doses. Time one dose 30-45 minutes pre-training. Endurance effects appear within 5-10 days in most reports. For pure aerobic sport performance, some users run SR-9009 as a standalone for WADA-tested competition preparation — note it is WADA-prohibited regardless of route.
Metabolic health / longevity: 10 mg/day sublingual (morning only) for 8-12 weeks. This lower dose is supported by the 2025 chronic low-dose study (10 mg/kg daily in mice reduced weight gain, insulin resistance, and white fat mass without the toxicity observed at high doses). At this dose, circadian rhythm disruption and insomnia risk are minimal. Useful as a circadian-alignment tool for shift workers or those with disrupted sleep/wake cycles — though the evidence is entirely preclinical.
Recomposition (stacked with SARMs): SR-9009 20-25 mg/day sublingual + Ostarine 15-20 mg/day. SR-9009 handles endurance and fat oxidation; Ostarine provides muscle-preserving anabolic input. This is a commonly reported stack that combines non-overlapping mechanisms with no receptor competition. Cycle length 8 weeks; Ostarine suppression will require PCT; SR-9009 does not.
Bulking cycle addition: SR-9009 20-30 mg/day added to an existing bulking cycle to limit fat accumulation. Enhanced mitochondrial efficiency and fat oxidation during a caloric surplus prevents disproportionate fat gain without blunting anabolic drive. Does not compete with androgenic compounds for any receptor.
Dosing Details
The bioavailability problem is the starting point for any SR-9009 dosing discussion. Animal pharmacokinetic data shows ~2.2% oral absorption in rats.
A 2013 study specifically testing three REV-ErbA agonists found 2.2% oral vs. 100% injectable bioavailability. The estimate sometimes cited for human oral bioavailability is ~24%, based on cross-species extrapolation — it is not derived from human PK data. A Scripps researcher reportedly stated oral bioavailability in humans may be close to zero. Community consensus: oral capsules are largely ineffective; the minority of users who report strong effects from oral SR-9009 may reflect unusually high exposure, product differences, or individual metabolic variation.
Half-life: 4-6 hours (based on mouse data). This pushes reported protocols toward multiple daily exposure windows rather than once-daily use.
Administration hierarchy in reports: Injectable and sublingual formats are generally treated as higher-exposure than oral capsules. Injectable reports often describe 10-20 mg/day split across the day, but the route adds sterility and irritation risks. Sublingual reports often describe 10-30 mg/day split into 2-3 doses, with better practical usability than repeated injections. Transdermal reports exist but are uncontrolled and vehicle-dependent. Oral capsule/powder reports are the least reliable; when oral use is discussed, it usually involves higher divided doses while acknowledging that most exposure may be lost.
Dose ranges by experience level: reported conservative ranges often start around 10-15 mg/day for sublingual/injectable formats and 20-30 mg/day for oral formats. Standard reports often cluster around 20-30 mg/day. More aggressive reports reach 30-40 mg/day, but doses above 40 mg/day are not supported by additional efficacy data and increase insomnia risk.
Timing: Reports consistently keep SR-9009 earlier in the day. A pre-workout exposure 30-45 minutes before training is reported to enhance session endurance, while late-day dosing is the most common sleep-disruption mistake.
Cycle length: 8-12 weeks is the community standard. SR-9009 is non-suppressive so there is no physiological necessity for a PCT-style limit, but cycling preserves efficacy and allows monitoring. Most users report an equal-length break after each cycle. No PCT required.
Preparation risk: Raw-powder or home injectable preparation creates infection, solvent, and concentration risks that can outweigh any route advantage. This article intentionally does not provide preparation instructions; the practical conclusion is that sterile, identity-confirmed presentation matters if injectable use is being considered at all.
Stacks & Alternatives
The canonical SR-9009 stack. Complementary non-overlapping pathways — REV-ErbA (circadian/mitochondrial) + PPARδ (fatty acid oxidation/gene expression). Both target fat-loss and endurance via different mechanisms; combined effect is additive. Cardarine's 24-hour half-life offsets SR-9009's demanding 3-4× daily dosing schedule.
Recomposition stack — SR-9009 covers fat oxidation and endurance enhancement; Ostarine provides modest anabolic muscle-preserving input without AR-driven suppression at moderate doses. Well-documented community combination for 8-week cut protocols.
Clean bulk variant — LGD provides anabolic mass; SR-9009 limits fat accumulation and improves training capacity during a surplus. No mechanism overlap. Requires PCT post-cycle for LGD suppression.
Recovery pairing — SR-9009 for performance/endurance; BPC-157 for connective tissue and gut healing. Frequently combined by long-cycle users who want both performance enhancement and injury resilience.
Alternatives
Stack Cost
SR-9009 creates moderate stack tax: it avoids androgenic suppression and PCT burden, but replaces that with route fragility, multiple daily dosing, sleep-timing discipline, WADA risk, liver/off-target uncertainty, and a total absence of human efficacy trials.
The article centers the 2.2% rat oral-bioavailability finding, the unverified human extrapolation, and the strong community split between oral non-response and sublingual/injectable response. Route choice determines whether the protocol is even worth judging.
The most consistent adverse effect is late-day insomnia or wired wakefulness. The practical rule is simple but unforgiving: finish dosing by 4-5 PM and keep stimulants away from the evening.
The efficacy case comes from rodent exercise/metabolic studies plus community translation, not human trials. The 2019 REV-ERB-independent mitochondrial-stress finding adds a real unknown that cannot be solved by standard bodybuilding lab panels.
The short 4-6 hour half-life pushes users toward 2-3 daily doses. Injectable use increases sterility burden; sublingual use is easier but still requires timing and solvent tolerance.
SR-9009 is WADA-prohibited and detectable via parent compound/metabolites. Any tested athlete has a hard exclusion independent of health risk.
- ·Oral capsules have high non-response risk; sublingual or injectable reports are more reliable but add route-specific burden.
- ·Finish all SR-9009 doses by 4-5 PM, and earlier for sleep-sensitive users.
- ·Do not combine with other REV-ERB agonists such as SR-9011 or SLU-PP-332.
- ·Treat Cardarine as a separate toxicology decision, not a free stack upgrade.
- ·Avoid use in WADA-tested contexts regardless of route or dose.
- ·Route-quality verification and third-party testing discipline before judging response.
- ·Baseline sleep log and dosing cutoff rule.
- ·Baseline LFTs, with midcycle LFTs for extended cycles, higher doses, or prior liver concerns.
- ·Explicit stop rule for persistent insomnia, headaches/nausea that do not settle, or ALT/AST above 3x ULN.
- ·Calendar that supports 2-3 daily doses without drifting into evening exposure.
SR-9009 is beginner-friendly only in the narrow sense that it is non-androgenic. The actual protocol punishes casual use: oral forms often fail, late dosing disrupts sleep, injectable use adds sterility risk, and the evidence base is not human-clinical.
- ·Using oral capsules and expecting reliable effects.
- ·WADA-tested or likely to be drug-tested.
- ·Already has insomnia, unstable sleep timing, shift-work circadian disruption, or stimulant-heavy evening habits.
- ·Taking warfarin, cyclosporine, antiretrovirals, or other narrow-therapeutic-index medication without clinician oversight.
- ·Attempting injectable preparation without sterile technique.
Standalone SR-9009 is non-suppressive and does not require PCT or tapering. The main off-ramp is stopping when sleep, headache/nausea, liver markers, or no-response makes the cost unjustified.
Do not judge SR-9009 from oral capsules alone; switch route before escalating dose aggressively.
Move the final dose earlier or reduce total daily dose; discontinue if sleep remains impaired.
Keep cycles bounded and avoid stacking redundant clock modulators; no human data means conservative exposure wins.
Use sterile technique and rotate sites; stop and medically evaluate expanding warmth, redness, swelling, or fever.
Most common problems are reversible timing/tolerance issues, but persistent sleep disruption, liver-enzyme movement, medication interactions, and injectable-site infection signs are not cosmetic.
Practical Setup
Form selection: Given the bioavailability problem, form selection is the single most important practical variable.
Injectable SR-9009 is treated as the reference standard for efficacy in community reports, but it adds sterility and injection-site risk. Sublingual liquid is the more practical high-bioavailability format. Oral capsules are the least reliable. Lab-verified purity via HPLC or MS testing is important regardless of format because underdosed and mislabeled products are documented in this space.
Storage: Keep products away from light and heat. Liquid and injectable preparations are more storage-sensitive than tablets or capsules, and poor handling can create apparent non-response.
Timing discipline is non-negotiable: SR-9009 exposure late in the day is the highest-leverage cause of sleep disruption. Users who "can't make SR-9009 work" without insomnia are often dosing too late rather than proving the compound is intolerable.
When protocols are adjusted in reports: If endurance improvements plateau after week 6, users usually consider adaptation, subthreshold exposure, or form failure before concluding true non-response. If sleep disruption persists despite early-day use, reports usually reduce total dose or move exposure earlier.
Injectable safety: Injectable SR-9009 raises sterility, solvent, and irritation concerns. Signs of infection such as swelling, warmth, redness expanding beyond the injection site, or systemic fever require medical attention. Home preparation is a high-risk lane and this article does not provide operational instructions for it.
Drug interactions: No documented pharmacokinetic drug interactions. REV-ErbA activation affects hepatic metabolizing enzyme expression — theoretical potential to alter CYP enzyme activity. This has not been characterized in humans. Caution with narrow-therapeutic-index drugs (warfarin, cyclosporine, antiretrovirals) where minor CYP changes could matter; avoid combining SR-9009 with such drugs without medical supervision.
WADA testing: SR-9009 and its metabolites are detectable in urine. Eight metabolites identified in human liver microsome studies; WADA screens for both parent compound and metabolites. Detection window from last dose: approximately 2-4 weeks based on metabolite half-lives, though this is not rigorously characterized. Do not use in competition contexts.
Mechanism Deep Dive
REV-ErbA nuclear receptors: the circadian-metabolic node
REV-ErbAα (NR1D1) and REV-ErbAβ (NR1D2) are nuclear hormone receptors that function as transcriptional repressors and heme sensors. They occupy a central role in the circadian feedback loop: they suppress transcription of BMAL1 and CLOCK — the positive regulatory arm of the circadian clock — creating the oscillating rhythm that drives ~24-hour biological cycles. Their endogenous ligand is heme (iron-containing porphyrin), which stabilizes their interaction with the corepressor complex NCOR1/HDAC3. SR-9009 mimics and amplifies this heme-bound active conformation, increasing the repressor activity of both REV-ErbAα and REV-ErbAβ.
IC50 values: 670 nM for REV-ErbAα, 800 nM for REV-ErbAβ (Solt et al., 2012). The compound is not fully selective — it activates both isoforms with similar potency.
Downstream metabolic effects via REV-ErbA activation
REV-ErbA represses a broad set of metabolic gene targets:
REV-ERB-independent effects (identified 2019)
Dierickx et al. (PNAS, 2019) generated conditional REV-ErbAα/β double-knockout mice and showed SR-9009 retains substantial biological activity in cells lacking both REV-ErbA isoforms:
The identification of REV-ERB-independent cytotoxic effects at 10 μM in cell models is a mechanistically important finding for the community. At standard community doses (20-30 mg/day sublingual), systemic concentrations are far below 10 μM, but the existence of off-target mechanisms — particularly mitochondrial stress induction — represents an uncharacterized dimension of SR-9009 pharmacology that has not been characterized in human tissues.
Pharmacokinetics
Evidence Index
Quantitative claims trace to these source studies. Population, dose, and study type matter — claims from HIV-lipodystrophy trials don't transfer cleanly to healthy adults; data from supraphysiologic doses doesn't apply at TRT.
Not medical advice. PepTutor summarizes fallible research and community signal for trained practitioners; some compounds are research-only, unapproved, controlled, jurisdiction-dependent, or labeled not for human consumption.