SR9009 (Stenabolic): The Complete Guide

SR9009 (Stenabolic) is a synthetic small-molecule Rev-erbα / Rev-erbβ dual agonist developed in the Burris lab at Scripps Florida. It is not a peptide and not a SARM — it’s a synthetic small molecule, despite living in peptide-adjacent vendor catalogs.

Founding paper:

PMID 22460951 — Solt LA, Wang Y, Banerjee S, et al. Nature 2012. “Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.” Original characterization of SR9009 + companion compound SR9011 as Rev-erb agonists with circadian and metabolic effects.

Regulatory status:

• FDA (US): not approved for any indication. No NDA, no IND. Sold gray-market as a research chemical.
• WADA 2026: prohibited at all times under S4 Hormone and Metabolic Modulators (specifically the metabolic-modulator subsection). Named explicitly as a Rev-erb agonist on the 2026 list (in force from January 1, 2026), alongside SR9011. Doping-control labs have produced certified reference materials specifically to detect SR9009 abuse (Davies 2019, PMID 30129998).

Nominal mechanism: Rev-erbα / Rev-erbβ agonism

Rev-erbα is a nuclear receptor that acts as a transcriptional repressor with strong roles in:

• Circadian rhythm — represses Bmal1, Npas2, Clock.
• Skeletal-muscle oxidative metabolism — high expression in oxidative muscle.
• Hepatic and adipose lipid metabolism.
• Inflammation regulation in macrophages.

SR9009 binds Rev-erbα/β as a synthetic agonist, enhancing the receptor’s repressor activity. Downstream effects (Solt 2012, PMID 22460951; Woldt 2013 Nature Medicine, PMID 23852339):

• Mitochondrial biogenesis in oxidative muscle.
• Increased running endurance via the Lkb1–AMPK–SIRT1–PGC-1α axis.
• Reduced fat mass, improved dyslipidemia and hyperglycemia in DIO mice.
• Reduced atherosclerotic plaque size in Ldlr−/− mice (Sitaula 2015, PMID 25800870).
• Selective killing of cancer cells and oncogene-induced senescent cells via autophagy / lipogenesis dysregulation (Sulli 2018, Nature, PMID 29320480).

The receptor-independence challenge (load-bearing)

PMID 31127047 — Dierickx P, Vermunt MW, Muraro MJ, et al. PNAS 2019 (Lazar lab at Penn). Tested SR9009 in cells genetically deleted for both Rev-erbα and Rev-erbβ. SR9009 retained substantial effects on cell viability, metabolism, and gene transcription in the receptor-knockout cells.

Translation: a meaningful fraction of SR9009’s biology is not mediated by its nominal target. The receptor itself (Rev-erbα) is still a legitimate target — but how much of SR9009-the-tool-compound’s effect runs through Rev-erb is now uncertain.

This matters for two reasons:

1. If SR9009 has substantial off-target activity, we don’t fully know what we’re looking for in long-term safety screens.
2. Vendor framing of "SR9009 is a Rev-erbα agonist that does X" overstates the certainty of the mechanism attribution.

Trump RP, Bresciani S, Cooper AWJ, et al. J Med Chem 2013. PMID 23656296. Title: “Optimized Chemical Probes for REV-ERBα.”

The Burris-lab follow-up paper characterizing SR9009 PK in rodents:

Parameter	SR9009	Source
Terminal half-life (t½)	~0.55 h (~33 min)	Trump 2013, PMID 23656296
Oral bioavailability (F%)	~2.2%	Trump 2013, PMID 23656296
Clearance	High (rapid metabolic clearance)	Trump 2013; Solt 2012

Practical implication: almost no oral capsule protocol in community use replicates the preclinical exposure that produced the published mouse effects. The Burris lab itself developed follow-up chemotypes (the Trump 2013 paper title is "Optimized Chemical Probes for REV-ERBα") precisely because the parent SR9009/SR9011 series had high clearance and low oral exposure.

Vendor protocols of "20–40 mg oral 3× daily" produce blood levels far below those used in the Solt 2012 / Woldt 2013 mouse studies (which used IP-dosed 100 mg/kg). Whatever results community users see at oral doses are not directly anchored to the published preclinical effect curves.

Claim	Evidence	Tier
Increases mitochondrial biogenesis in oxidative muscle	Solt 2012 PMID 22460951; Woldt 2013 PMID 23852339	Preclinical mouse, IP-dosed
Improves running endurance (mice)	Woldt 2013 PMID 23852339	Preclinical mouse, IP-dosed
Reduces fat mass / improves metabolic syndrome (mice)	Solt 2012 PMID 22460951	Preclinical mouse, IP-dosed
Reduces atherosclerotic plaque (mice)	Sitaula 2015 PMID 25800870	Preclinical mouse
Selectively kills cancer cells / senescent cells	Sulli 2018 PMID 29320480	Preclinical / in vitro / mouse
"Cardarine without the cancer risk"	None	Unsupported — no long-term human safety data; receptor-independence challenge means we don’t even know what off-target signal to look for
Human exercise capacity / endurance	None	No published human trial
Human fat loss / body composition	None	No published human trial

Rule of thumb: almost every benefit claim for SR9009 should land at "preclinical, mouse, IP-dosed." Anything stronger is overreach. Any claim that implies the SR9009 effect is definitely mediated through Rev-erbα should also acknowledge the Dierickx 2019 receptor-independence finding.

The PK numbers above mean any oral SR9009 protocol is unanchored to the published preclinical effect data. The community dosing below is what users actually do; it is not what the science supports.

Parameter	Common Range
Dose	20–40 mg oral 3× daily (community)
Total daily	60–120 mg
Cycle length	4–12 weeks (community)
Route	Oral (despite F% ~2.2%); some users inject SC for higher exposure

Half-life ~33 minutes means even multi-daily oral dosing produces only brief plasma exposure. SC injection achieves higher exposure but isn’t how the published mouse studies dosed (those were IP).

No published human safety data. All concerns below are mechanism-anchored or animal-anchored.

Acute concerns:

• Sleep disruption / circadian desynchronization — SR9009 enhances Rev-erb repression of Bmal1 and other clock genes; community users report disrupted sleep with evening dosing.
• GI upset (community).
• Mood / cognitive changes (community).

Chronic / theoretical:

• Off-target effects. Per Dierickx 2019, SR9009 has substantial Rev-erb-independent activity. By definition we don’t know what those off-target hits do over months of human dosing.
• Cancer / autophagy. Sulli 2018 reported SR9009 selectively kills cancer cells via autophagy disruption — but autophagy is essential in normal tissues too. Chronic autophagy inhibition has cardiac, neuronal, and immune liabilities.
• Cardiac. Rev-erbα has documented cardiac roles. Chronic agonism effects on cardiac function are uncharacterized in humans.
• Immune. Rev-erbα regulates macrophage inflammation; chronic agonism could shift inflammatory balance.

• Pregnancy / breastfeeding — no data.
• Active or prior cancer — mixed signal: Sulli 2018 selective-killing data is in vitro / mouse; chronic autophagy disruption in normal tissue is theoretical concern.
• Cardiovascular disease — class concern.
• Sleep disorders / shift work — SR9009 disrupts the circadian clock by design.
• Concurrent stimulants / sleep medication — uncharacterized interactions.
• Athletes subject to anti-doping testing — do not use. WADA S4 names SR9009 explicitly; certified reference materials exist for detection.

• Cardarine (GW501516) — PPARδ agonist, completely different receptor target. Cardarine has documented multi-organ rodent carcinogenicity that GSK pulled the program over. Vendor framing of "SR9009 = safer Cardarine" is unsupported (no long-term tox study has been done for SR9009).
• SR9011 — companion compound from Solt 2012, similar pharmacology, similar PK problems.
• AICAR — AMPK activator (different mechanism, also exercise-mimetic framing).
• 5-Amino-1MQ — NNMT inhibitor (different mechanism).
• SLU-PP-332 — ERRβ/γ agonist, different receptor; another exercise-mimetic class candidate.
• MOTS-c — mitochondrial-derived peptide; different family entirely but adjacent “exercise mimetic” framing.