If you have been reading about circadian rhythm and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-01-21. Where a claim depends on a specific study, the study is described rather than over-claimed.
Preclinical reports have linked SR9009 to improved endurance and altered energy expenditure in rodents. Such findings have prompted interest in whether REV-ERB activation can influence skeletal muscle metabolism. However, the reported effects depend on dose, route, and experimental model, and replication across laboratories is limited. Human trials have not established comparable outcomes, so claims about exercise performance remain speculative. The absence of controlled human data is a central limitation in interpreting these observations.
The mechanism of action involves binding to REV-ERB receptors and recruiting corepressor complexes, which represses target gene transcription. This contrasts with many nuclear receptor agonists that activate transcription. Downstream effects may include changes in autophagy, mitochondrial biogenesis, and lipid handling, but the precise pathways remain an active area of study. Whether these molecular events translate into meaningful physiological effects in humans is unresolved. Most evidence comes from cultured cells and rodent models rather than human participants.
SR9009 is a synthetic small molecule developed as an agonist of the nuclear receptors REV-ERBα (NR1D1) and REV-ERBβ (NR1D2). These receptors help regulate circadian rhythms and metabolic gene expression. In cell and animal studies, SR9009 alters transcription of genes involved in lipid metabolism, inflammation, and mitochondrial function. It is not an approved medicine, and its pharmacological profile in humans remains largely uncharacterized. The compound is frequently discussed in the context of circadian biology and metabolic research rather than clinical use.
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.
Because REV-ERB receptors are core clock components, SR9009 has been examined for effects on daily rhythms as well as metabolism. Research has explored whether the compound can shift or reinforce circadian gene expression in tissues such as liver and muscle. Some studies report improved metabolic markers in obese or diabetic mice, while others show context-dependent responses. Questions remain about which effects are direct, which are secondary to timing, and how they might differ across species.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic REV-ERB agonist | Small molecule; not a steroid or peptide. |
| Primary targets | NR1D1 and NR1D2 | Also known as REV-ERBα and REV-ERBβ. |
| Studied routes | Intraperitoneal in rodents | Oral bioavailability in humans is not established. |
| Human approval | No approved therapeutic indication | No recognized clinical use. |
| Key uncertainty | Human physiological effects | Preclinical findings may not translate. |
Storage recommendations for SR9009 reference material typically specify a freezer at -20 °C or lower, with protection from moisture and light. Repeated freeze-thaw cycles can degrade small molecules and introduce variability. Stock solutions in dimethyl sulfoxide are often aliquoted to avoid repeated handling. Stability studies may examine degradation under heat, humidity, and light exposure. The compound's thiophene and nitro groups can participate in reactions that alter analytical signals over time, so such changes affect quantitative results.
Quality control for research materials includes identity confirmation by nuclear magnetic resonance and purity assessment by high-performance liquid chromatography. Mass spectrometry provides molecular weight confirmation and can detect related impurities. Purchasers should request a certificate of analysis that lists lot-specific data. Online products advertised for human use often lack such documentation. Distinguishing legitimate research material from mislabeled or contaminated samples is a recurring challenge in independent testing, and independent laboratories may use orthogonal methods to verify identity.
Detection of SR9009 in biological samples usually relies on liquid chromatography coupled to tandem mass spectrometry. This approach separates the compound from matrix components and identifies it by mass transitions. Because SR9009 can undergo metabolism, laboratories often look for both parent drug and specific metabolites. Sample preparation may involve protein precipitation or solid-phase extraction. Method validation examines sensitivity, carryover, and interference from related substances, and reference standards are required for accurate calibration.
Laboratory studies often administer SR9009 by injection because oral absorption appears poor in rodents. Reported pharmacokinetic properties include rapid metabolism and low systemic exposure after oral dosing. Human pharmacokinetic data are sparse, so absorption, distribution, metabolism, and excretion in people are not well defined. Some research explores related REV-ERB compounds with improved drug-like properties. Regulatory approval for any REV-ERB agonist as a human medicine has not been granted to date.
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.
Regulatory status varies by country and intended use. Major drug agencies have not granted marketing authorization for SR9009 as a medicine, and it is not listed as a controlled substance in many jurisdictions. It is often sold as a research chemical, a category that may fall outside pharmaceutical manufacturing rules. Buyers should verify local laws and supplier documentation, including certificates of analysis. The lack of standardized quality controls raises concerns about identity, purity, and actual content in products marketed online.
In laboratory settings, SR9009 is commonly identified by its molecular structure and its interaction with REV-ERB receptors. Vendors may list it under synonyms such as Stenabolic or REV-ERB agonist, but those names do not define purity or identity. Analytical confirmation typically uses high-performance liquid chromatography with ultraviolet detection or liquid chromatography–mass spectrometry. A reference standard is needed to compare retention time and mass spectrum, because the compound can be confused with related research chemicals.
==== Signaling bias ==== Main section: § Signaling dynamics Many functional differences between KOR agonists can be explained by biased signaling, whereby different agonists preferentially activate distinct signaling pathways downstream of the receptor. Evidence suggests that G protein signaling primarily mediates the therapeutic analgesic and antipruritic effects of KOR agonists, whilst β-arrestin2-dependent signaling through p38 MAPK activation mediates adverse dysphoric, sedative, and aversive effects.
== Biosynthesis == Apigenin is biosynthetically derived from the general phenylpropanoid pathway and the flavone synthesis pathway. The phenylpropanoid pathway starts from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the Shikimate pathway. When starting from L-phenylalanine, first the amino acid is non-oxidatively deaminated by phenylalanine ammonia lyase to make cinnamate, followed by oxidation at the para position by cinnamate 4-hydroxylase to produce p-coumarate. As L-tyrosine is already oxidized at the para position, it skips this oxidation and is simply deaminated by tyrosine ammonia lyase to arrive at p-coumarate. To complete the general phenylpropanoid pathway, 4-coumarate CoA ligase substitutes coenzyme A at the carboxy group of p-coumarate. Entering the flavone synthesis pathway, the type III polyketide synthase enzyme chalcone synthase uses consecutive condensations of three equivalents of malonyl-CoA followed by aromatization to convert p-coumaroyl-CoA to chalcone. Chalcone isomerase then isomerizes the product to close the pyrone ring to make naringenin. Finally, a flavanone synthase enzyme oxidizes naringenin to apigenin. Two types of flavone synthase (FNS) have been described; FNS I, a soluble enzyme that uses 2-oxogluturate, Fe2+, and ascorbate as cofactors and FNS II, a membrane bound, NADPH dependent cytochrome p450 monooxygenase.
Elementary schools in Prince George's County operate in several configurations, ranging from Pre-K (Head Start) through grade 6. Most elementary schools operate under a kindergarten through grade 6 configuration, and lack a pre-kindergarten/Head Start program. More recently, with boundary realignments to ease overcrowding and with the opening of newer and larger schools and increased funding, several schools have changed to a PreK-6th grade configuration while others have added a Pre-kindergarten, but dropped the sixth grade, to change to a Pre-K through grade 5 school. The sixth grades from those schools were added to the elementary schools' feeder middle schools. In a cooperative effort of the county government, board of education, and the Maryland National Capital Park & Planning Commission (M-NCPPC), several M-NCPPC community centers are physically connected to elementary schools, throughout the district. The unique community park/school centers features shared use areas which include a gymnasium, multi-purpose room, exercise/fitness room, dance room, arts and crafts room, computer lab, offices, storage areas, patio area, and restrooms. Tennis courts and unlighted fields are located on-site at select centers.
Sources: en.wikipedia.org
Risk of developing CJD increases with age. CJD incidence was 3.5 cases per million among those over 50 years of age between 1979 and 2017. Approximately 85% of CJD cases are sporadic, and 10–15% of CJD cases are due to inherited mutations of the prion protein gene. CJD deaths and age-adjusted death rate in the United States indicate an increasing trend in the number of deaths between 1979 and 2017. Although not fully understood, additional information suggests that CJD rates in nonwhite groups are lower than in whites. While the mean onset is approximately 67 years of age, cases of sCJD have been reported as young as 17 years and over 80 years of age. Mental capabilities rapidly deteriorate and the average amount of time from onset of symptoms to death is 7 to 9 months. According to a 2020 systematic review on the international epidemiology of CJD:
Some MAAs protect cells from reactive oxygen species (i.e. singlet oxygen, superoxide anions, hydroperoxyl radicals, and hydroxyl radicals). Reactive oxygen species can be created during photosynthesis; further supporting the idea that MAAs provide protection from UV light. Mycosporine-glycine is a MAA that provides antioxidant protection even before Oxidative stress response genes and antioxidant enzymes are induced. MAA-glycine (mycosporine-glycine) is able to quench singlet oxygen and hydroxyl radicals very quickly and efficiently. Some oceanic microbial ecosystems are exposed to high concentrations of oxygen and intense light; these conditions are likely to generate high levels of reactive oxygen species. In these ecosystems, MAA-rich cyanobacteria may be providing antioxidant activity.
== Design precautions == If sufficient reactivity control authority is available, the reactor can be restarted, but a xenon burn-out transient must be carefully managed. As the control rods are extracted and criticality is reached, neutron flux increases many orders of magnitude and the 135Xe begins to absorb neutrons and be transmuted to 136Xe. The reactor burns off the nuclear poison. As this happens, the reactivity increases and the control rods must be gradually re-inserted or reactor power will increase. The time constant for this burn-off transient depends on the reactor design, power level history of the reactor for the past several days (therefore the 135Xe and 135I concentrations present), and the new power setting. For a typical step up from 50% power to 100% power, 135Xe concentration falls for about 3 hours. The first time 135Xe poisoning of a nuclear reactor occurred was on September 28, 1944, in Pile 100-B at the Hanford Site. The B Reactor was a plutonium production reactor built by DuPont as part of the Manhattan Project. The reactor was started on September 27, 1944, but the power dropped unexpectedly shortly after, leading to a complete shutdown on the evening of September 28. Next morning the reaction restarted by itself. The physicists John Archibald Wheeler, working for DuPont at the time, and Enrico Fermi were able to identify that the drop in the neutron flux and the consequent shutdown was caused by the accumulation of 135Xe in the reactor fuel.
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of cancer, neurodegeneration, apoptosis, regulating sleep, and much more. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures. There is lot of potential in the Hsp70 protein as a key therapeutic target for developing new drugs for the treatment of sleep disorders, cancer, neurodegeneration, and other related pathological conditions.
Sources: en.wikipedia.org
It is a synthetic compound that acts as an agonist at REV-ERBα and REV-ERBβ. It is used mainly as a research chemical to study circadian and metabolic pathways. It is not approved for human therapeutic use.
REV-ERB receptors generally repress transcription when bound by natural heme. SR9009 is described as an agonist that enhances this repressive activity. The result is altered expression of clock and metabolic genes.
Published controlled human trials are lacking. Some sources cite limited or unofficial reports, but these do not establish safety or efficacy. Claims about human performance effects remain unverified.
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.