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Background And Receptor Mechanism — 2026 Update

By Editorial Desk · published 2025-11-16 · last reviewed 2025-12-16 · Faq

REV-ERB agonist raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.

Reviewed 2025-12-16. Anything still debated is marked as such rather than presented as settled.

Background and Receptor Mechanism

SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ, also called NR1D1 and NR1D2. These receptors help regulate circadian rhythms and metabolic gene programs. The compound was developed for laboratory research, not as an approved therapeutic. Its identity is distinct from steroid hormones and selective androgen receptor modulators. Scientific interest centers on how REV-ERB activation changes gene expression in cells and animal models.

At the molecular level, SR9009 binds the ligand-binding domain of REV-ERB and strengthens recruitment of corepressor proteins such as NCoR and HDAC3. This increases repression of target genes, including Bmal1 and other clock-controlled and metabolic genes. In rodent studies, such changes have been linked to altered lipid handling, glucose metabolism, and energy expenditure. The precise chain of events between receptor binding and whole-body effects remains an active area of research. Findings in animals do not automatically translate to humans.

SR9009 Background and Receptor Mechanism

SR9009 is a synthetic small molecule studied as an agonist of REV-ERB nuclear receptors. REV-ERB alpha and REV-ERB beta help regulate circadian rhythms and metabolic gene expression. In laboratory research, SR9009 has been used to probe how these receptors affect skeletal muscle, liver, and adipose tissue. The compound was identified in academic drug-discovery work and is often described in scientific literature by its chemical name and research code. It is not an approved medicine, and human clinical data remain limited or absent.

SR9009 binds REV-ERB receptors and alters their repressive activity on target genes. This action can change transcription of genes involved in lipid handling, glucose metabolism, and mitochondrial function. In rodent studies, treated animals have shown changes in muscle oxidative capacity and exercise performance, though effects vary by dose, duration, and model. The precise molecular steps connecting receptor binding to whole-body outcomes are still an active area of investigation. Findings in animals do not automatically translate to humans.

Sr9009 at a glance

PropertyValueNotes
Chemical classSynthetic small moleculeStudied as a REV-ERB agonist
Molecular formulaC20H24ClN3O4SReported for the neutral compound
AppearanceOff-white to pale yellow solidTypical research-grade material
SolubilitySparingly soluble in waterSoluble in solvents such as DMSO
Common synonymsSR9009; StenabolicStenabolic is an informal alias

Analytical Detection and Laboratory Handling

Physicochemical behavior influences handling. SR9009 is described as a solid with limited aqueous solubility, so organic solvents such as dimethyl sulfoxide or ethanol are common in research stock solutions. Aqueous dilution can produce precipitates if the organic content is too low. Light, heat, and repeated freeze-thaw cycles may affect stability. Storage recommendations usually specify a desiccated freezer environment protected from light, but exact stability data depend on the formulation and matrix.

Detection in biological samples can be complicated by rapid metabolism and low circulating concentrations. Some studies report phase I and phase II metabolites, and analytical methods may need to target those species in addition to the parent compound. Immunoassays are not broadly available, so mass spectrometry remains the main confirmatory approach. For anti-doping testing, laboratories look for SR9009 and its metabolites using validated LC-MS methods. Open questions include how long metabolites remain detectable and how different routes of administration alter detection windows.

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Analytical and Handling Considerations

For long-term storage, SR9009 is typically kept as a solid at low temperature, protected from moisture and light. Desiccated conditions limit hydrolysis, while opaque containers reduce photochemical breakdown. Solutions are less stable than solids and are often stored frozen in aliquots to avoid repeated freeze-thaw cycles. Stability data are not standardized across all suppliers, so users should rely on certificate-of-analysis information when available. Degradation may appear as color change, precipitate, or decreased chromatographic purity.

Laboratory identification of SR9009 typically relies on chromatographic separation coupled to mass spectrometry, often with ultraviolet detection as a secondary check. Nuclear magnetic resonance spectroscopy can confirm molecular structure when a reference standard is available. Because many suppliers sell the compound as a research chemical, independent identity testing is important for experimental reproducibility. A single retention time is not sufficient proof of identity, especially when related compounds may be present. Purity assessments usually report a percentage based on area normalization.

SR9009 is generally described as poorly soluble in water and more soluble in organic solvents such as dimethyl sulfoxide and ethanol. Stock solutions are commonly prepared in an organic solvent before dilution into an aqueous buffer or vehicle. Precipitation can occur if the organic fraction is reduced too quickly or if the final concentration exceeds the compound's solubility limit. Sonication or gentle warming may aid dissolution in some protocols, but excessive heat can promote degradation. Container material and pH can also influence observed solubility.

Supporting material

== Awards and honors == 1990 - Robert J. and Claire Pasarow Foundation Medical Research Award 1990 - American Association for Cancer Research - G.H.A. Clowes Memorial Award Archived 2017-10-24 at the Wayback Machine 1991 - Honorary doctorate in medicine from Lund University, Sweden 1995 - Nobel Fellow at the Karolinska Institutet in Stockholm 1997 - Gairdner Foundation International Award 1998 - Jacobaeus International Prize 2003 - Jubilee Lecturer, Biochemical Society 2005 - Japan Prize in Cell Biology 2012 - Thomson Reuters Citation Laureate Knight of the Order of the White Rose of Finland Commander of the Order of the Lion of Finland 2022 - Albert Lasker Award for Basic Medical Research. 2023 - Fellow of the American Association for Cancer Research. Member of National Academy of Sciences National Academy of Medicine American Academy of Arts and Sciences European Molecular Biology Organization

Food plays various roles in social and cultural life. In Chinese folk religion, ancestor veneration is conducted by offering food to ancestors and Chinese festivals involve the consumption and preparation of specific foods which have symbolic meanings attached to them. Specific religions in China have their own cuisines such as the Taoist diet, Buddhist cuisine and Chinese Islamic Cuisine. The Kaifeng Jews in Henan province once had their own Chinese Jewish cuisine but the community has largely died out in the modern era and not much is known about the specifics of their cuisine but they did influence foods eaten in their region and some of their dishes remain. Chinese dishes with purported Kaifeng Jewish roots include Kaifeng xiao long bao, Mayuxing bucket-shaped chicken, Chrysanthemum hot pot, and Four Treasures. Food also plays a role in daily life. The formality of the meal setting can signify what kind of relationship people have with one another, and the type of food can indicate ones' social status and their country of origin. In a formal setting, up to sixteen of any combination of hot and cold dishes would be served to respect the guests. On the other hand, in a casual setting, people would eat inexpensive meals such as at food stalls or homemade food. The typical disparity in food in the Chinese society between the wealthy and everyone below that group lies in the rarity and cost of the food or ingredient, such as shark fins and bear paws.

July 1971: The association "Choisir la cause des femmes" is created — with philosopher Simone de Beauvoir and lawyer Gisèle Halimi — to demand the repeal of the 1920 law criminalizing abortion. January 3, 1972: Law on parentage. It opens the right for the mother to challenge, under certain conditions, the presumption of the husband's paternity. January 3, 1972: Law on the stay-at-home mother's allowance. April 24, 1972: Decree applying Article 4 of Law 67-1176 of December 28, 1967, on birth control and repealing Articles L. 648 and L. 649 of the Public Health Code. July 13, 1972: Law establishing the general status of military personnel; access to military careers is not subject to sex-based discrimination. August 16, 1972: Decree on the specific status of the corps of national police inspectors, in which women are allowed to apply. December 22, 1972: Law affirming the principle of equal pay between genders. January 2, 1973: Law on the Labor Code, which updates it and includes provisions on women's work. January 9, 1973: Law amending and supplementing the French Nationality Code and concerning certain provisions related to French nationality; it notably authorizes the transmission of nationality by the mother to her child, whether the child is "legitimate or illegitimate." March 23, 1973: Decree establishing the special status of female military corps.

Sources: en.wikipedia.org

Notes from published material

In 1961, Peter Mitchell proposed chemiosmosis as a cell's primary system of energy conversion. The mechanism, now ubiquitous in living cells, powers energy conversion in micro-organisms and in the mitochondria of eukaryotes, making it a likely candidate for early life. Mitochondria produce adenosine triphosphate (ATP), the energy currency of the cell used to drive cellular processes such as chemical syntheses. The mechanism of ATP synthesis involves a closed membrane in which the ATP synthase enzyme is embedded. The energy required to release strongly bound ATP has its origin in protons that move across the membrane. In modern cells, those proton movements are caused by the pumping of ions across the membrane, maintaining an electrochemical gradient. In the first organisms, the gradient could have been provided by the difference in chemical composition between the flow from a hydrothermal vent and the surrounding seawater, or perhaps meteoric quinones that were conducive to the development of chemiosmotic energy across lipid membranes if at a terrestrial origin.

Militaries have long had risk-reduction procedures for their troops to follow, and studies are in consistent agreement that veterans who used DU-enhanced munitions have not suffered, so far, from an increased risk of cancer (see the Gulf War and Balkans sections below). The effects of DU on civilian populations are, however, a topic of intense and ongoing controversy. As early as 1997, British Army doctors warned the Ministry of Defence that exposure to depleted uranium increased the risk of developing lung, lymph and brain cancer, and recommended a series of safety precautions. According to a report issued summarizing the advice of the doctors, "Inhalation of insoluble uranium dioxide dust will lead to accumulation in the lungs with very slow clearance—if any. ... Although chemical toxicity is low, there may be localised radiation damage of the lung leading to cancer." The report warns that "All personnel ... should be aware that uranium dust inhalation carries a long-term risk ... [the dust] has been shown to increase the risks of developing lung, lymph and brain cancers." In 2003, the Royal Society called, again, for urgent attention to be paid to the possible health and environmental impact of depleted uranium, and added its backing to the United Nations Environment Programme's call for a scientific assessment of sites struck with depleted uranium. In early 2004, the UK Pensions Appeal Tribunal Service attributed birth defect claims from a February 1991 Gulf War combat veteran to depleted uranium poisoning.

== Adverse effects == As with other SGLT2 inhibitors, canagliflozin is associated with increased incidence of urinary tract infections, fungal infections of the genital area, thirst, elevations in LDL cholesterol, increased urination and episodes of low blood pressure. Rarely, use of canagliflozin is associated with necrotizing fasciitis of the perineum, also called Fournier gangrene. There are concerns that it may also increase the risk of diabetic ketoacidosis. Possible cardiovascular problems are an ongoing issue with gliflozin drugs. The pre-specified endpoint for cardiovascular safety in the canagliflozin clinical development program was "Major Cardiovascular Events Plus", defined as the occurrence of cardiovascular death, non-fatal myocardial infarctions, non-fatal strokes, or unstable angina leading to hospitalization. This endpoint occurred in more people in the placebo group (20.5%) than in the canagliflozin treated group (18.9%). Nonetheless, a United States Food and Drug Administration (FDA) advisory committee expressed concern regarding the cardiovascular safety of canagliflozin. A greater number of cardiovascular events was observed during the first 30 days in study subjects who received canagliflozin (0.45%) compared those who received placebo (0.07%), suggesting an early period of increased cardiovascular risk. In addition, there was an increased risk of stroke in subjects who received canagliflozin. However, none of these effects were statistically significant. Additional cardiovascular safety data from another ongoing study are expected in 2015.

Silent mutations, also called synonymous or samesense mutations, are mutations in DNA that do not have an observable effect on the organism's phenotype, as they produce the same amino acid though a single base pairing has been altered. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality (e.g. a mutation producing leucine instead of isoleucine) are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.

Sources: en.wikipedia.org

Further detail

== Allowed health claims == Governmental regulatory agencies stipulate for the food and dietary supplement industries certain health claims as allowable as statements on packaging. Europe: European Food Safety Authority (EFSA)

==== NATO involvement ==== The North Atlantic Treaty Organization (NATO) has played a role in addressing the issue of drug trafficking, particularly in Afghanistan, as part of its broader security and stabilization efforts. NATO has supported counter-narcotics initiatives by assisting the Afghan government in building its capacity to combat the illegal drug trade, which is seen as a major source of funding for insurgent groups. NATO's efforts include training and equipping Afghan security forces to enhance their ability to disrupt drug trafficking networks, as well as supporting intelligence-sharing and coordination with international partners. These activities are framed within NATO's mission to promote stability and security, recognizing the link between the drug trade and threats to regional and global security. However, perspectives on NATO's involvement in counter-narcotics operations have varied, with some reports highlighting tensions with other international actors, such as the United Nations. While NATO emphasizes its contributions to reducing the drug trade through capacity-building and support for Afghan-led initiatives, other sources have noted discrepancies in reported outcomes, suggesting that the drug trade in Afghanistan remained robust despite these efforts. For instance, data from 2012 indicates that opium production continued to thrive, raising questions about the effectiveness of NATO's strategies in this domain.

=== Detection methods === Mass spectrometry (MS) is used to identify and quantify metabolites after optional separation by GC, HPLC, or CE. GC-MS was the first hyphenated technique to be developed. Identification leverages the distinct patterns in which analytes fragment. These patterns can be thought of as a mass spectral fingerprint. Libraries exist that allow identification of a metabolite according to this fragmentation pattern . MS is both sensitive and can be very specific. There are also a number of techniques which use MS as a stand-alone technology: the sample is infused directly into the mass spectrometer with no prior separation, and the MS provides sufficient selectivity to both separate and to detect metabolites. For analysis by mass spectrometry, the analytes must be imparted with a charge and transferred to the gas phase. Electron ionization (EI) is the most common ionization technique applied to GC separations as it is amenable to low pressures. EI also produces fragmentation of the analyte, both providing structural information while increasing the complexity of the data and possibly obscuring the molecular ion. Atmospheric-pressure chemical ionization (APCI) is an atmospheric pressure technique that can be applied to all the above separation techniques. APCI is a gas phase ionization method, which provides slightly more aggressive ionization than ESI which is suitable for less polar compounds.

=== Pharmacodynamics === Flmodafinil is a selective dopamine reuptake inhibitor (DRI). Its affinity (Ki) for the DAT is 4,090 nM. At the serotonin transporter (SERT), its affinity (Ki) was 48,700 nM (12-fold lower than for the DAT), and it had negligible affinity for the sigma σ1 receptor (Ki > 100,000 nM). The drug has been found to block the dopamine transporter (DAT) by 83%, to a greater extent than methylphenidate without unfavorable concomitant adrenergic effects. The drug is an atypical DRI similarly to modafinil. The affinities for the DAT of flmodafinil's enantiomers and modafinil have also been studied. The affinities (Ki) were 5,480 nM for armodafinil ((R)-modafinil), 2,970 nM for (S)-(+)-flmodafinil (JBG1-048), and 4,830 nM for (R)-(–)-flmodafinil (JBG1-049). Their affinities for the SERT and σ1 receptor have also been reported. Similarly to modafinil, (S)-(+)-flmodafinil and (R)-(–)-flmodafinil increase dopamine levels in the nucleus accumbens in animals. They have been found to increase dopamine levels by up to 150 to 200% of baseline at the highest assessed dose. These increases are much smaller than those elicited by amphetamine or cocaine. In a study comparing the wake-promoting effects of flmodafinil and modafinil, flmodafinil was found to maintain wakefulness over a significantly longer timeframe than modafinil. While the administration of neither compound resulted in sleep rebound, flmodafinil perturbed sleep architecture to a lesser degree than modafinil.

In May 2000, the GSI successfully repeated the experiment to synthesize a further atom of copernicium-277. This reaction was repeated at RIKEN using the Search for a Super-Heavy Element Using a Gas-Filled Recoil Separator set-up in 2004 and 2013 to synthesize three further atoms and confirm the decay data reported by the GSI team. This reaction had also previously been tried in 1971 at the Joint Institute for Nuclear Research in Dubna, Russia to aim for 276Cn (produced in the 2n channel), but without success. Work had also been done there from 1998 to synthesize the heavier isotope 283Cn in the hot fusion reaction 238U(48Ca,3n)283Cn; most observed atoms of 283Cn decayed by spontaneous fission, although an alpha decay branch to 279Ds was detected. While initial experiments aimed to assign the produced nuclide with its observed long half-life of 3 minutes based on its chemical behaviour, this was found to be not mercury-like as would have been expected (copernicium being under mercury in the periodic table), and indeed now it appears that the long-lived activity might not have been from 283Cn at all, but its electron capture daughter 283Rg instead, with a shorter 4-second half-life associated with 283Cn.

Sources: en.wikipedia.org

Frequently asked questions

What is SR9009?

SR9009 is a synthetic research compound that activates the REV-ERBα and REV-ERBβ nuclear receptors. It is not an approved drug and has no established human therapeutic use. Most published biological data come from cell and rodent studies.

Is SR9009 a SARM?

No. SR9009 is frequently mislabeled as a SARM in online discussions, but it does not target androgen receptors. Its known mechanism involves REV-ERB nuclear receptors and circadian-metabolic gene regulation.

What human data exist for SR9009?

Human clinical data are very limited. There is no approved human use, and safety and efficacy in people are not established. Most evidence comes from preclinical models, so effects observed in animals may not apply to humans.

What is SR9009?

SR9009 is a synthetic research compound that acts on REV-ERB nuclear receptors. It is not approved for human use and is sold only as a research chemical. Its effects have been studied mainly in cells and rodents.

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