Rev-erb-alpha agonist (not a SARM)

Our opinion on this compoundNiche research probe

51/100

The canonical Rev-erb-alpha probe with genuine circadian-metabolic bench utility but near-zero translational signal

Look, SR-9009 occupies a specific and genuinely useful niche in circadian and metabolic research. It’s the canonical Rev-erb-alpha agonist, which means if you’re building a research program around circadian clock genes and their downstream metabolic effects, this is your compound. That matters. But the score here is held firmly in the low-50s by a set of problems that any serious investigator needs to confront before putting this on the bench.

The mechanism is legitimately interesting. Rev-erb-alpha sits at the intersection of circadian regulation and metabolic gene expression, with downstream effects on fatty acid oxidation pathways, BMAL1/CLOCK transcriptional machinery, and inflammatory gene suppression. The Burris group at Scripps (the same group that developed SR-9009) demonstrated real exercise capacity and body composition effects in mouse models, and the target biology is active enough that independent groups have continued using the compound as a probe to dissect this circuit. That’s the good news.

Here’s the problem: the pharmacokinetics are genuinely rough. Oral bioavailability in rodents is under 5 percent. The Scripps data that generated all the excitement was intraperitoneal. Thats a meaningful caveat for any translational read, and it’s the kind of thing that separates serious preclinical work from the popular hype that followed. You can’t take IP rodent data with a compound this poorly absorbed and draw confident lines toward human biology. There are no human clinical trials for SR-9009. None. The translational gap here is not theoretical, its structural.

What saves SR-9009’s research value is exactly what it was designed for: utility as a tool compound. If you’re studying how Rev-erb-alpha agonism affects lipid catabolism, glucose homeostasis, or the transcriptional output of the circadian clock machinery, SR-9009 is your best available probe. GSK4112 and SR-9011 exist in the same space, but SR-9009 has the most extensive associated literature and remains the reference compound most labs reach for. On that axis alone, it earns its place on a serious research bench.

The evidence base is also concentrated. Burris group papers dominate the foundational claims, with independent work using SR-9009 as a tool rather than actively validating those claims from scratch. Multi-lab preclinical use exists, but the primary efficacy data hasn’t been tested in humans, and the bioavailability issue creates real uncertainty about how much of the rodent signal survives any route-compatible translation attempt. We think SR-9009 is worth having in a library focused on circadian-metabolic biology. It’s a real probe for a real target with active research interest. But dont confuse probe utility with therapeutic candidate status; the score reflects exactly that distinction.

Novelty: 50
Mechanism promise: 60
In-category differentiation: 68
Evidence quality: 38
Translational signal: 20
Research bench value: 70

Rationale SR-9009 scores primarily on differentiation and bench value as the go-to Rev-erb-alpha agonist for circadian biology research, but the combination of no human clinical data, sub-5% oral bioavailability in rodents, and a Scripps-dominated literature base holds the overall score firmly in the low-50s.

Rev-erb-alpha agonist (not a SARM)

A Rev-erb-alpha agonist developed for circadian and metabolic disorders; popularly grouped with SARMs but mechanistically distinct.

Abstract

Stenabolic (SR-9009; CAS 1379686-30-2; molecular formula C20H24ClN3O4S; molecular weight 437.94) is a synthetic Rev-erb-alpha agonist developed by Burris and colleagues at Scripps Research Institute. Rev-erb-alpha is a nuclear receptor with circadian regulation function; pharmacological agonism shifts metabolic gene expression toward fatty acid oxidation and reduces inflammatory gene transcription. Mouse studies demonstrated improved exercise capacity and body composition with intraperitoneal dosing, generating substantial popular interest. The compound has poor oral bioavailability (less than 5 percent in rodents), making the recreational oral use pattern pharmacologically inconsistent with the published in vivo data. SR-9009 is not approved by any regulatory authority and has no human clinical trial record. Plasma half-life is approximately 4 hours after IP dosing in rodents. Used as the canonical Rev-erb-alpha agonist in academic circadian and metabolic research.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Tag: Rev-erb-alpha agonist (not a SARM)

Stenabolic (SR-9009)

Abstract

Read the full monograph