Stenabolic

Technical data

INN name

Stenabolic

Development code

SR9009

Identity and composition

Stenabolic is the common name for SR9009 (Stenabolic), a synthetic small molecule that acts as an agonist of the nuclear receptors REV-ERB. It is not a peptide: it is an organic compound of the pyrrolidine-carboxylate type, studied only at the preclinical and research level.

Its chemical identity is confirmed in PubChem (CID 57394020):

• CAS: 1379686-30-2
• Molecular formula: C20H24ClN3O4S
• Molecular weight: 437.9 g/mol
• IUPAC name: ethyl 3-[[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]pyrrolidine-1-carboxylate
• Synonyms: SR9009, SR-9009, Stenabolic

As it is a small molecule and not a peptide, it has no amino acid sequence. Presentation of this sheet: 10 mg × 100 tablets.

Product for research use.

Mechanism of action

Stenabolic (SR9009) is described in the literature as a synthetic agonist of the REV-ERB nuclear receptors (REV-ERBα/NR1D1 and REV-ERBβ/NR1D2). These receptors are transcriptional repressors of the circadian clock; their pharmacological activation suppresses the expression of Bmal1 and other clock genes and remodels the circadian expression of metabolic genes in the liver, skeletal muscle, and adipose tissue. In the foundational mouse study, following the administration of SR9009, an increase in oxygen consumption and energy expenditure was observed (Solt LA et al., Nature 2012; PMID 22460951).

An important nuance for interpreting its mechanism: later literature showed that SR9009 produces effects independent of REV-ERB on cell viability, metabolism, and transcription, even in cells with deletion of both REV-ERBα/β. Therefore, its effects should not be attributed exclusively to REV-ERB activity (Dierickx P et al., PNAS 2019; PMID 31127047).

Pharmacokinetics

The specific pharmacokinetic parameters are not confirmed in open primary sources for this listing. The literature describes a extensive hepatic metabolism, with multiple metabolites identified in hepatic microsomes by means of LC-HRMS, but concrete values of half-life (t½) or oral bioavailability were not verified here. A relevant point for the tablet form: the preclinical efficacy studies used parenteral administration (intraperitoneal), and in the general literature a low oral bioavailability is reported for SR9009, although this datum was not confirmed in an open primary source in this research.

Scientific evidence

The available evidence on Stenabolic is preliminary, exclusively preclinical and limited. It comes from animal (mouse) and in vitro models; no human clinical trials were identified for SR9009 as a therapeutic. In exploratory preclinical studies it has been investigated in contexts of obesity and diet-induced metabolic disease, insulin resistance, weight gain from circadian disruption, and in oncology cell lines in vitro (e.g., T98G glioblastoma).

In the foundational work in mice, an increase in oxygen consumption and energy expenditure was observed, along with remodeling of circadian metabolic genes (Solt LA et al., Nature 2012; PMID 22460951). There is also a considerable body of anti-doping literature (in vitro metabolism, reference materials, detection in urine/plasma), which reflects its status as a substance prohibited in sport rather than an approved therapeutic indication. No regulatory authority has approved it for clinical use.

Research applications

Product for research use.

Suitable for:

• In vitro and animal-model studies on the biology of REV-ERB receptors and the circadian clock.
• Exploratory research in energy metabolism, circadian signaling and preclinical metabolic models.
• Analytical and forensic work (detection methods, metabolite characterization, anti-doping control).

Not applicable for:

• clinical use, clinical use, diagnostic or therapeutic use of any kind.
• Sports use: it is a substance subject to anti-doping control and prohibited in sport.
• Any application that assumes results in humans: there are no clinical trials supporting efficacy or safety in people.

Research protocols

In the consulted literature no verified numerical doses are available used in studies, so no specific milligram figures or quantitative regimens are reported.

What is qualitatively documented: the preclinical efficacy studies used parenteral route (intraperitoneal) in mouse models, not oral administration (Solt LA et al., Nature 2012; PMID 22460951). This contrasts with the commercial tablet presentation. Any research protocol design must be defined according to the experimental model, the route of administration and the corresponding primary literature, without extrapolating to humans.

Reconstitution

This presentation corresponds to 10 mg oral tablets of a small molecule, not a lyophilized powder. Therefore, does not require reconstitution with bacteriostatic water or with other diluents: the tablets are used as is in the research context.

As a general laboratory reference: reconstitution with bacteriostatic water (water with ~0.9% benzyl alcohol as a preservative) applies to lyophilized vials, not to oral solid forms such as this one. To prepare working solutions from solid material for analytical purposes, one resorts to the standard solvents and procedures of the corresponding experimental method.

Stability and storage

As a standard laboratory-handling guide for a small molecule in solid form (tablets):

• Store in its original packaging, closed, protected from light and humidity.
• Keep in a cool, dry place; refrigerated storage can prolong the stability of the solid material.
• Avoid repeated humidity/temperature cycles and prolonged exposure to air.

Note: SR9009 possesses a nitrothiophene group and presents extensive metabolization described in the literature, so it is advisable to minimize exposure to light and heat. These indications are for general laboratory handling; they do not substitute the stability validation specific to each protocol.

Safety profile

The safety profile of Stenabolic is not characterized in humans: there are no safety data from clinical trials, and no regulatory authority has approved it for clinical use.

Considerations documented at the preclinical and in vitro level:

• Off-target effects: SR9009 reduces cell viability and alters metabolism and transcription independently of REV-ERB, which complicates the interpretation of both its mechanism and its safety (Dierickx P et al., PNAS 2019; PMID 31127047).
• Anti-doping control: is a substance prohibited in sport, with abundant forensic work dedicated to its detection.

As it is a research compound, it must be handled with standard laboratory precautions (personal protective equipment, avoid inhalation and ingestion). It is not intended for clinical use.

Comparative context

Stenabolic (SR9009) is usually studied together with SR9011, a structural analog that also acts as a REV-ERB agonist and whose pharmacokinetic profile is reported in the literature as more favorable.

A frequent point of commercial confusion: SR9009 is sometimes grouped with the SARMs (selective androgen receptor modulators), but does not share its mechanism. SR9009 does not act on the androgen receptor; its target is the nuclear receptors REV-ERB, linked to the circadian clock and metabolism. It is, therefore, a distinct pharmacological class.

Another relevant difference: its marketing as an oral tablet contrasts with the parenteral route (intraperitoneal) used in the preclinical efficacy studies.

History and development

Stenabolic emerges as SR9009 (Stenabolic), a small synthetic molecule developed as an agonist of the REV-ERB nuclear receptors to investigate the role of these receptors in the circadian clock and metabolism. Its foundational characterization was published in the mouse study by Solt and colleagues, where it was described as a synthetic REV-ERB agonist and its effects on bioenergetics and on the circadian expression of metabolic genes were documented (Solt LA et al., Nature 2012; PMID 22460951).

Subsequently, research expanded and nuanced its profile by demonstrating REV-ERB-independent effects (Dierickx P et al., PNAS 2019; PMID 31127047). In parallel, an extensive body of anti-doping literature focused on its metabolism and detection was developed. To date it remains an exclusively preclinical, research-use compound, without regulatory approval for clinical use.

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Scientific references (2)

Peer-reviewed literature on Stenabolic, with its PubMed identifier where available:

• Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists (Solt, et al. · Nature · 2012) PMID 22460951.
• SR9009 induces a REV-ERB dependent anti-small-cell lung cancer effect through inhibition of autophagy (Shen, et al. · Theranostics · 2020) PMID 32292508.

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