circadian rhythm is one of those subjects where the details matter more than the headlines. This page pulls together the background, the mechanisms, and the practical points readers ask about most.
Last reviewed on 2025-07-24. Where a claim depends on a specific study, the study is described rather than over-claimed.
SR9009 is a synthetic small molecule studied as a REV-ERB agonist. REV-ERBα and REV-ERBβ are nuclear receptors that help regulate circadian rhythms and metabolic gene expression. The compound was identified in academic screening efforts to find synthetic ligands for these receptors. In cell and animal studies, SR9009 alters transcription of genes involved in lipid and glucose metabolism, and it can shift circadian behavior. It is not an approved therapeutic agent.
Mechanistically, SR9009 binds the ligand-binding domain of REV-ERBα/β and enhances recruitment of corepressor complexes. This represses target genes rather than activating them. Because REV-ERB proteins normally compete with ROR proteins at shared response elements, the net effect depends on tissue and timing. Researchers use SR9009 to probe how nuclear receptor signaling links the clock to metabolism, inflammation, and muscle biology. Findings are largely preclinical, and the precise contribution of each receptor subtype remains under study.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic REV-ERB agonist | Small-molecule ligand; not a hormone or peptide |
| Molecular formula | C20H24ClN3O4S | Reported for the free base |
| CAS Registry Number | 1379686-30-2 | Unique chemical identifier |
| Common synonyms | SR9009; stenabolic | Stenabolic is informal and not an official name |
| Reported targets | REV-ERBα and REV-ERBβ | Nuclear receptors linked to circadian and metabolic regulation |
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.
In laboratory settings, SR9009 is typically characterized by liquid chromatography–mass spectrometry (LC-MS) or high-performance liquid chromatography with ultraviolet detection (HPLC-UV). These methods can confirm identity and estimate purity, but they require reference standards for accurate quantification. Because SR9009 is not a licensed pharmaceutical, no harmonized pharmacopeial monograph exists. Laboratories often validate in-house methods for matrices such as plasma, urine, or cell culture media. Sample preparation may involve protein precipitation or liquid-liquid extraction before analysis.
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.
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.
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.
nucleobase Sometimes used interchangeably with nitrogenous base or simply base. Any of the five primary or canonical nitrogenous bases – adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U) – that form nucleosides and nucleotides, the latter of which are the fundamental building blocks of nucleic acids. The ability of these bases to form base pairs via hydrogen bonding, as well as their flat, compact three-dimensional profiles, allows them to "stack" one upon another and leads directly to the long-chain structures of DNA and RNA. When writing sequences in shorthand notation, the letter N is often used to represent a nucleotide containing a generic or unidentified nucleobase.
== Occurrence == The most abundant polyphenols are the condensed tannins, found in virtually all families of plants. Larger polyphenols are often concentrated in leaf tissue, the epidermis, bark layers, flowers and fruits but also play important roles in the decomposition of forest litter, and nutrient cycles in forest ecology. Absolute concentrations of total phenols in plant tissues differ widely depending on the literature source, type of polyphenols and assay; they are in the range of 1–25% total natural phenols and polyphenols, calculated with reference to the dry green leaf mass. Polyphenols are also found in animals. In arthropods, such as insects, and crustaceans polyphenols play a role in epicuticle hardening (sclerotization). The hardening of the cuticle is due to the presence of a polyphenol oxidase. In crustaceans, there is a second oxidase activity leading to cuticle pigmentation. There is apparently no polyphenol tanning occurring in arachnids cuticle.
=== 9 May === Two people were killed by Russian shelling in Nikopol. In Russia, the governor of Belgorod Oblast claimed that eight people were injured in a Ukrainian airstrike in Belgorod city. A drone attack on Krasnodar also set a fuel depot on fire. A drone strike was also reported in an oil refinery in Salavat in the first such incident of its kind in the constituent republic of Bashkortostan. The drone used in the attack on Bashkiria was conducted by a drone light aircraft, make unknown, that travelled some 1,500 km. The SBU arrested a resident of Kharkiv on suspicion of spying for Russia. It also claimed to have arrested several individuals in Kyiv on suspicion of attempting to set off bombs on behalf of Russia. Zelenskyy implemented a number of changes in the Ukrainian defense apparatus. He appointed Brigadier General Oleksandr Trepak as commander of the Ukrainian Special Operations Forces, replacing Colonel Serhii Lupanchuk. He also dismissed Valeriy Zaluzhnyi, former commander-in-chief of Ukraine's Armed Forces, from military service "on health grounds", and reappointed Dmytro Hereha as the commander of the Ukrainian Support Forces after replacing him with Oleksandr Yakovets in March 2024. Zelenskyy also dismissed Serhii Rud as director of the State Security Administration. Two colonels were also arrested after being accused of being agents for the Russian FSB. The US Army announced that it would supply three additional HIMARS units paid for by Germany to Ukraine.
Immunology/Serology uses the process of antigen-antibody interaction as a diagnostic tool. Compatibility of transplanted organs may also be determined with these methods. Immunohematology, or blood bank determines blood groups, and performs compatibility testing on donor blood and recipients. It also prepares blood components, derivatives, and products for transfusion. This area determines a patient's blood type and Rh status, checks for antibodies to common antigens found on red blood cells, and cross matches units that are negative for the antigen. Urinalysis tests urine for many analytes, including microscopically. If more precise quantification of urine chemicals is required, the specimen is processed in the clinical biochemistry lab. Histopathology processes solid tissue removed from the body (biopsies) for evaluation at the microscopic level. Cytopathology examines smears of cells from all over the body (such as from the cervix) for evidence of inflammation, cancer, and other conditions. Molecular diagnostics includes specialized tests involving DNA and RNA analysis. Cytogenetics involves using blood and other cells to produce a DNA karyotype. This can be helpful in cases of prenatal diagnosis (e.g. Down's syndrome) as well as in some cancers which can be identified by the presence of abnormal chromosomes. Surgical pathology examines organs, limbs, tumors, fetuses, and other tissues biopsied in surgery such as breast mastectomies.
Sources: en.wikipedia.org
Doxepin is a highly potent antihistamine, with this being its strongest activity. In fact, doxepin has been said to be the most or one of the most potent H1 receptor antagonists available, with one study finding an in vitro Ki of 0.17 nM. It is the most potent and selective H1 receptor antagonist of the TCAs (although the tetracyclic antidepressant (TeCA) mirtazapine is slightly more potent), and other sedating antihistamines, for instance the over-the-counter diphenhydramine (Ki = 16 nM) and doxylamine (Ki = 42 nM), show far lower affinities for this receptor in comparison. The affinity of doxepin for the H1 receptor is far greater than its affinity for other sites, and 10- to 100-fold higher doses are needed for antidepressant effects. In accordance, although it is often described as a "dirty drug" due to its highly promiscuous binding profile, doxepin acts as a highly selective antagonist of the H1 receptor at very low doses (less than 10 mg; typically 3 to 6 mg). At these doses, it notably has no clinically relevant anticholinergic effects such as dry mouth or cognitive/memory impairment, unlike most other sedating antihistamines, and similarly has no effect on other receptors such as adrenergic and serotonin receptors. The H1 receptor antagonism of doxepin is responsible for its hypnotic effects and its effectiveness in the treatment of insomnia at low doses.
=== Impeachment of Sara Duterte === In December 2024, Duterte offered to join the defense team of his daughter, Vice President Sara Duterte, against her impeachment. On February 18, 2025, two weeks after the vice president was impeached by the House of Representatives, Duterte was listed as the legal counsel of his daughter in her Supreme Court petition to stop the impeachment from proceeding to trial.
Proposed mitigation strategies include factoring potential environmental costs prior to model development or data collection, increasing efficiency of data centers to reduce electricity/energy usage, building more efficient machine learning models, minimizing the number of times that models need to be retrained, developing a government-directed framework for auditing the environmental impact of these models, regulating for transparency of these models, regulating their energy and water usage, encouraging researchers to publish data on their models' carbon footprint, and increasing the number of subject matter experts who understand both machine learning and climate science.
== Detoxification == To prevent the toxic effects, AzM can be biotransformed. Although AzM (in figure 2 named guthion) can be bioactivated by a cytochrome P450 (CYP450)-mediated desulfuration to its phosphate triester or oxon (gutoxon), it may also be detoxified by CYP itself (reaction 2 in figure 2). CYP450 is namely able to catalyze the oxidative cleavage of the P-S-C bond in AzM to yield DMTP and MMBA. The other pathways of detoxification involves glutathione (GSH)-mediated dealkylation via cleavage of the P-O-CH3 bond, which than forms mono-demethylated AzM and GS-CH3 (reaction 3 in figure 2). This mono-demethylated AzM may be further demethylated to di-demethylated AzM and again GS-CH3 (reaction 4 in figure 2). AzM also may undergo glutathione-catalyzed dearylation which forms DMPDT and glutathione-conjugated mercaptomethyl benzazimide (reaction 5 in figure 2) Gutoxon, the compound that mainly causes AzM to be toxic, can also be detoxified. Gutoxon can again be detoxified with the help of CYP450. CYP450 catalyzes the oxidative cleavage of gutoxon, which than yields DMP and MMBA (reaction 6 in figure 2). Other detoxification pathways of gutoxon are via glutathione-mediated dealkylation, which goes via cleavage of the P-O-CH3 bond to form demethylated AzM and GS-CH3 (reaction 7 in figure 2), and via glutathione-catalyzed dearylation to yield DMTP and glutathione-conjugated mercaptomethyl benzazimide (reaction 8 in figure 2).
In March 2025, the company sold its entire stake in Haleon for $3.24 billion to institutional investors. In October 2025, Pfizer entered an agreement with the Trump administration to voluntarily lower US drug prices, which included a three-year exemption from pharmaceutical-specific tariffs, as long as the firm further invests in domestic manufacturing. Pfizer pledged to put $70 billion into US manufacturing and research. In November 2025, Pfizer acquired Metsera to expand its weight-loss drug portfolio in a deal that had the potential to exceed $10 billion.
Sources: en.wikipedia.org
SR9009 is a synthetic compound investigated as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is used in preclinical research on circadian rhythm and metabolism. It is not an approved drug.
No. It has no approved medical indication, and human safety and efficacy data are limited. It appears in research chemical markets and is banned by some sports authorities.
Natural ligands include heme and certain metabolites; SR9009 is a synthetic small molecule with higher potency and selectivity in some assays. Its effects depend on cell type and timing. It is not a naturally occurring compound.
Liquid chromatography with mass spectrometry is a common approach. Ultraviolet detection and nuclear magnetic resonance can support identification when suitable standards are available.