Everything below concerns nuclear receptor. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-07-23. Numbers and descriptions here follow the published literature rather than marketing material.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is not an approved medicine and has no established human therapeutic use. The compound appears in scientific literature as a tool for probing circadian and metabolic regulation. Online sellers often label it as a research chemical, sometimes using the nickname Stenabolic. Its chemical identity is distinct from selective androgen receptor modulators, stimulants, and peroxisome proliferator-activated receptor delta agonists. Researchers use it mainly in cell and animal experiments.
At the molecular level, SR9009 binds REV-ERBα and REV-ERBβ and alters their repressive activity on target genes. These nuclear receptors help regulate the circadian clock, lipid synthesis, glucose metabolism, and inflammatory pathways. By changing transcription, the compound can shift the timing or magnitude of downstream metabolic processes in model systems. It does not act through androgen receptors or adenosine receptors, which distinguishes it from several substances sold for athletic performance. Whether the same transcriptional changes occur in humans at tolerable exposures remains an open question because controlled human studies are lacking.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. These receptors help regulate circadian rhythms, lipid metabolism, and inflammatory gene expression. In cell and animal experiments, SR9009 alters transcription of clock-controlled genes and metabolic pathways. The compound is not a hormone and does not resemble classical steroid structures. Its activity depends on binding to the ligand-binding domain of REV-ERB, where it can modify corepressor recruitment.
Research interest in SR9009 grew from studies of circadian biology and metabolic disease. Preclinical reports describe effects on exercise capacity, muscle metabolism, and blood lipid levels in rodents, but these findings come from controlled laboratory settings. The compound has low oral bioavailability in animals, which limits systemic exposure after swallowing. Investigators often use injected routes in experiments to achieve measurable plasma concentrations. Human clinical data are sparse, no approved therapeutic product exists, and whether animal effects translate to humans remains an open question.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C20H24ClN3O4S | Derived from published structure. |
| Molecular weight | 437.94 g/mol | Calculated value. |
| Appearance | White to off-white solid | Typical for purified research samples. |
| Solubility | DMSO, ethanol; low in water | Class: poorly water-soluble. |
| Typical storage | -20 °C, desiccated, protected from light | Limits degradation. |
In rodent studies, SR9009 has been reported to increase mitochondrial content in skeletal muscle and improve exercise endurance under some conditions. These findings led to popular descriptions such as an exercise mimetic, although that term oversimplifies the biology. Effects vary by dose, timing, tissue, and model. The compound's influence on circadian pathways means that time of administration can matter in experiments. Whether similar metabolic changes occur in humans remains largely unexplored in controlled published trials.
Pharmacokinetic data for SR9009 are limited in published literature. Some reports indicate low oral bioavailability and rapid clearance in animals, which complicates interpretation of exposure and effect. Researchers often use injected routes in preclinical work to achieve measurable systemic levels. Analytical studies rely on mass spectrometry to detect the parent compound and its metabolites. Questions about tissue distribution, active metabolites, and long-term consequences remain open. Species differences in metabolism can affect observed half-life and target engagement.
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.
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.
Chronic social defeat stress produces a counterintuitive long-lasting downregulation of prodynorphin mRNA levels in the NAcc (occurring by day 10 of chronic exposure), and this downregulation is reversed by chronic treatment with standard antidepressant medication (imipramine). Despite this molecular downregulation, behavioral signs of stress-induced dysphoria, anhedonia, and anxiety persist and even intensify with repeated stress exposure, indicating that the coupling between dynorphin release and KOR phosphorylation, as well as the downstream consequences of KOR activation, may become sensitized through counter-adaptations in post-receptor signaling or in competing inhibitory circuits. This process involves: § Signaling after internalisation.
== Effect on central nervous system == Opioid receptors, located in both the central nervous system as well as peripheral tissues, play a vital role in regulating numerous physiological functions. Many of these functions are influenced by exorphins. To impact the central nervous system, exorphins bind to opioid receptors, thereby regulating neuronal communication. This binding affects pain perception, emotions, mood, memory, and more. The influence of exorphins on brain function suggests that exogenous opioid peptides may cross the blood-brain barrier. This understanding of how endorphins enter through blood and end up affecting brain functions could pave the way for the development of new treatment strategies.
=== Lifestyle === Weight loss is the most effective treatment for MASLD and MASH. A loss of 5% to 10% body weight is recommended and has shown regression of liver damage, with 10% to 40% weight loss completely reversing MASH without cirrhosis. A weight loss of greater than 10% was associated with the resolution of MASH in 90% of people in a biopsy-based study. A structured weight loss program helps people with MASLD lose more weight compared with advice alone. This type of program also leads to improvements in MASLD measured by blood tests, ultrasound, imaging, or liver biopsies. Although fibrosis improves with lifestyle interventions and weight loss, there is limited evidence for improvement in cirrhosis. A combination of improved diet and exercise, rather than either alone, appears to help manage MASFLD and reduce insulin resistance. Motivational support, such as with cognitive behavioral therapy, is helpful, as most people with MASLD do not perceive their condition as a disease, and thus have a low motivation to change. Higher-intensity behavioral weight loss therapies (diet and exercise combined) may produce greater weight loss than lower-intensity ones. A 2019 systematic review suggested updating the guidelines to recommend these therapies for MASLD management. Weight loss is associated with improvements in biomarkers, MASLD severity, and a lower risk of MASH, but its effect on long-term health is not known.
Sources: en.wikipedia.org
=== Nervous system and senses === Octopuses and their relatives have a more expansive and complex nervous system than other invertebrates, containing over 500 million neurons, around the same as a dog. One part is localised in the brain, contained in a cartilaginous capsule. Two-thirds of the neurons are in the nerve cords of its arms. This allows their arms to perform actions with a degree of independence. Learning mainly occurs in the brain, while arms make decisions independently when supplied with information. A severed arm can still move and respond to stimuli. Unlike in many other animals, including other molluscs, the movement of octopuses and their relatives are not organised in their brains via internal somatotopic maps of their bodies. Octopuses have the same jumping genes that are active in the human brain, implying an evolutionary convergence at molecular level.
An epitope, () also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes. The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation. 90% of epitopes are conformational.
=== HPLC-based === A faster method of log P determination makes use of high-performance liquid chromatography. The log P of a solute can be determined by correlating its retention time with similar compounds with known log P values. An advantage of this method is that it is fast (5–20 minutes per sample). However, since the value of log P is determined by linear regression, several compounds with similar structures must have known log P values, and extrapolation from one chemical class to another—applying a regression equation derived from one chemical class to a second one—may not be reliable, since each chemical classes will have its characteristic regression parameters.
== Further reading == Sigel, Roland K. O.; Skilandat, Miriam; Sigel, Astrid; Operschall, Bert P.; Sigel, Helmut (2013). "Chapter 8. Complex formation of cadmium with sugar residues, nucleobases, phosphates, nucleotides and nucleic acids". In Sigel, Astrid; Sigel, Helmut; Sigel, Roland K. O. (eds.). Cadmium: From Toxicology to Essentiality (PDF). Metal Ions in Life Sciences. Vol. 11. Springer. pp. 191–274. doi:10.1007/978-94-007-5179-8_8. ISBN 978-94-007-5178-1. PMID 23430775. Sóvágó, Imre; Várnagy, Katalin (2013). "Chapter 9. Cadmium(II) complexes of amino acids and peptides". In Sigel, Astrid; Sigel, Helmut; Sigel, Roland K. O. (eds.). Cadmium: From Toxicology to Essentiality. Metal Ions in Life Sciences. Vol. 11. Springer. pp. 275–302. doi:10.1007/978-94-007-5179-8_9. ISBN 978-94-007-5178-1. PMID 23430776. Yatsimirsky, Konstantin Borisovich; Vasilyev, Vladimir Pavlovich (1960). Instability Constants of Complex Compounds. Translated by Patterson, D. A. OUP.
Sources: en.wikipedia.org
The lightweight chain of a bicycle with derailleur gears can snap (or rather, come apart at the side-plates, since it is normal for the "riveting" to fail first) because the pins inside are not cylindrical, they are barrel-shaped. Contact between the pin and the bushing is not the regular line, but a point which allows the chain's pins to work its way through the bushing, and finally the roller, ultimately causing the chain to snap. This form of construction is necessary because the gear-changing action of this form of transmission requires the chain to both bend sideways and to twist, but this can occur with the flexibility of such a narrow chain and relatively large free lengths on a bicycle. Chain failure is much less of a problem on hub-geared systems since the chainline does not bend, so the parallel pins have a much bigger wearing surface in contact with the bush. The hub-gear system also allows complete enclosure, a great aid to lubrication and protection from grit.
=== Argentina === The Armed Forces of the Argentine Republic's combat ration (Spanish: Ración de Combate (Individual)) was introduced in 2003, consisting of a gray plastic-foil laminate pouch containing a mix of canned and dehydrated foods, plus minimal supplements, for one soldier for one day. All products in the RC are domestically produced, commercially available items. Each ration contains canned meat, small can of meat spread, crackers, instant soup, cereal bar with fruit, a chocolate bar with nuts or caramels, instant coffee, orange juice powder, sugar, salt, a heating kit with disposable stove and alcohol-based fuel tablets, disposable butane lighter, resealable plastic bag, cooked rice, and a pack of paper tissues. Menu #1 contains corned beef, meat pâté, crisp water crackers, and instant soup with fideo pasta. Menu #2 contains roasted beef in gravy, meat pâté, whole wheat crackers, and quick-cooking polenta in cheese sauce.
=== Opposition to the Award === Basuto chiefs—including Lerotholi—welcomed the Award, and 3,000 heads of cattle were paid almost immediately as a gesture of goodwill. On 9 May 1881, Thomas Charles Scanlen replaced Sprigg as prime minister, while Basutophile Jacobus Wilhelmus Sauer was appointed as the new Secretary for Native Affairs. Scanlen encountered challenges in fully enforcing the Award, such as the erosion of the colonial administration's prestige. Masopha demanded to be granted almost arbitrary power, refusing to pay his share of the hut tax and forbidding the return of the local magistrate. Joseph Orpen, who replaced Griffith, was seen as too sympathetic to the former rebels. His handling of cattle and land compensation led to the alienation of Basuto loyalists and the departure of nearly all pre-war magistrates from Basutoland. In January 1882, Letsie I assembled an army in order to enforce the Award on Masopha, yet the expedition was cancelled as it was judged that Masopha retained considerable popular support. The Colonial Office refused to allow the Cape to abandon Basutoland and cancel the Award. Robinson then set 15 March as the new deadline for the enforcement of the Award, threatening to confiscate land from the chiefs failing to abide to it and to redistribute Quthing District to white volunteers who fought in the war. Following pleas by Letsie I and Orpen, Robinson cancelled the Award on 15 March and pledged not to confiscate land. This was followed by the repeal of the Peace Preservation Act on 6 April.
Sources: en.wikipedia.org
SR9009 is a synthetic REV-ERB agonist used in laboratory research. It is not an approved drug, and its effects in humans are not well characterized. It is often sold as a research chemical under the name Stenabolic.
No. SR9009 targets the nuclear receptors REV-ERBα and REV-ERBβ, not the androgen receptor. This mechanism differs from selective androgen receptor modulators and from exercise mimetics that act on PPARδ.
Published evidence is mainly preclinical, using cell cultures and animal models. Controlled human trials are not well documented in the public literature. Claims about human performance or health effects therefore remain unsupported by robust clinical data.
SR9009 is a synthetic small molecule studied as an agonist of the REV-ERB nuclear receptors. It is not an approved medicine, and its effects in humans are not well characterized.