This is a working overview of SR9009, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-12-01. Anything still debated is marked as such rather than presented as settled.
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.
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.
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.
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.
| 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. |
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.
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.
==== Liver toxicity ==== Although rare, flutamide has been associated with severe hepatotoxicity and death. By 1996, 46 cases of severe cholestatic hepatitis had been reported, with 20 fatalities. There have been continued case reports since, including liver transplants and death. A 2021 review of the literature found 15 cases of serious hepatotoxicity in women treated with flutamide, including 7 liver transplantations and 2 deaths. Based on the number of prescriptions written and the number of cases reported in the MedWatch database, the rate of serious hepatotoxicity associated with flutamide treatment was estimated in 1996 as approximately 0.03% (3 per 10,000). However, other research has suggested that the true incidence of significant hepatotoxicity with flutamide may be much greater, as high as 0.18 to 10%. Flutamide is also associated with liver enzyme elevations in up to 42 to 62% of patients, although marked elevations in liver enzymes (above 5 times upper normal limit) occur only in 3 to 5%. The risk of hepatotoxicity with flutamide is much higher than with nilutamide or bicalutamide. Lower doses of the medication appear to have a possibly reduced but still significant risk. Liver function should be monitored regularly with liver function tests during flutamide treatment. In addition, due to the high risk of serious hepatotoxicity, flutamide should not be used in the absence of a serious indication. The mechanism of action of flutamide-induced hepatotoxicity is thought to be due to mitochondrial toxicity.
The feeding activity of the omnivorous starfish Oreaster reticulatus on sandy and seagrass bottoms near the Virgin Islands effects the composition of communities of microorganisms. These starfish engulf piles of sediment removing the surface films and algae adhering to the particles. Organisms that dislike this disturbance are replaced by others better able to rapidly recolonise "clean" sediment. In addition, foraging by these starfish creates diverse patches of organic matter, which may attract larger organisms such as fish, crabs and sea urchins that feed on the sediment. Starfish sometimes have negative effects on ecosystems. Outbreaks of crown-of-thorns starfish have caused damage to coral reefs in Northeast Australia and French Polynesia. A study in Polynesia found that coral cover declined drastically with the arrival of migratory starfish in 2006, dropping over 40% to under 5% in four years. This in turn had a cascade effect on both sessile bottom-dwelling animals and reef fish. Asterias amurensis is a rare example of an invasive echinoderm. Its larvae likely arrived in Tasmania from central Japan via water discharged from ships in the 1980s. The species has since grown in numbers to the point where they threaten important bivalve fisheries in Australia. As such, they are considered pests, and are on the Invasive Species Specialist Group's list of the world's 100 worst invasive species. Some species that prey on bivalve molluscs can transmit paralytic shellfish poisoning.
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Sources: en.wikipedia.org
== Pace-of-play initiatives == As a part of pace-of-play initiatives implemented in 2015, 20-second pitch clocks entered use at Double-A stadiums in 2015. In 2018, the time was shortened to 15 seconds when no runners are on base. Other significant changes implemented in 2018 included beginning extra innings with a runner on second base and limiting teams to eight mound visits during a nine-inning game. In 2019, the number of mound visits was reduced to seven, and pitchers were required to face a minimum of three consecutive batters, unless the side is retired or the pitcher is injured and unable to continue.
Therefore, it has been hypothesized that the presence of supercritical CO2 in Hadean hydrothermal vents played an important role in the origin of life. There is some evidence that links the origin of life to alkaline hydrothermal vents in particular. The pH conditions of these vents may have made them more suitable for emerging life. One current theory is that the naturally occurring proton gradients at these deep sea vents supplemented the lack of phospholipid bilayer membranes and proton pumps in early organisms, allowing ion gradients to form despite the lack of cellular machinery and components present in modern cells. There is some discourse around this topic. It has been argued that the natural pH gradients of these vents playing a role in the origin of life is actually implausible. The counter argument relies, among other points, on what the author describes as the unlikelihood of the formation of machinery which produces energy from the pH gradients found in hydrothermal vents without/before the existence of genetic information. This counterpoint has been responded to by Nick Lane, one of the researchers whose work it focuses on. He argues that the counterpoint largely misinterprets both his work and the work of others. Another reason that the view of deep sea hydrothermal vents as an ideal environment for the origin of life remains controversial is the absence of wet-dry cycles and exposure to UV light, which promote the formation of membranous vesicles and synthesis of many biomolecules.
Each T cell expresses clonal TCRs which recognize a specific peptide loaded on a MHC molecule (pMHC), either on MHC class II on the surface of antigen-presenting cells or MHC class I on any other cell type. A unique feature of T cells is their ability to discriminate between peptides derived from healthy, endogenous cells and peptides from foreign or abnormal (e.g. infected or cancerous) cells in the body. Antigen-presenting cells do not discriminate between self and foreign peptides and typically express a large number of self-derived pMHCs on their cell surface and only a few copies of any foreign pMHC. For example, cells infected with HIV have only 8–46 HIV-specific pMHCs, compared with 100,000 total pMHCs, per cell. Because T cells undergo positive selection in the thymus, there is a non-negligible affinity between self-pMHC and the TCR. Nevertheless, the T-cell receptor signaling should not be activated by self-pMHC so that endogenous, healthy cells are ignored by T cells. However, when these very same cells contain even minute quantities of pathogen-derived pMHC, T cells must get activated and initiate immune responses. The ability of T cells to ignore healthy cells but respond when these same cells express a small number of foreign pMHCs is known as antigen discrimination. To do so, T cells have a very high degree of antigen specificity, despite the fact that the affinity to the peptide/MHC ligand is rather low in comparison to other receptor types.
Sources: en.wikipedia.org
=== Allies and Associated Powers === The declaration was first endorsed by a foreign government on 27 December 1917, when Serbian Zionist leader and diplomat David Albala announced the support of Serbia's government in exile during a mission to the United States. The French and Italian governments offered their endorsements in 1918. At a private meeting in London on 1 December 1918, Lloyd George and French Prime Minister Georges Clemenceau agreed to certain modifications to the Sykes–Picot Agreement, including British control of Palestine. On 25 April 1920, the San Remo conference – an outgrowth of the Paris Peace Conference attended by the prime ministers of Britain, France and Italy, the Japanese Ambassador to France, and the United States Ambassador to Italy – established the basic terms for three League of Nations mandates: a French mandate for Syria, and British mandates for Mesopotamia and Palestine. With respect to Palestine, the resolution stated that the British were responsible for putting into effect the terms of the Balfour Declaration. The French and the Italians made clear their dislike of the "Zionist cast of the Palestinian mandate" and objected especially to language that did not safeguard the "political" rights of non-Jews, accepting Curzon's claim that "in the British language all ordinary rights were included in "civil rights"". At the request of France, it was agreed that an undertaking was to be inserted in the mandate's procès-verbal that this would not involve the surrender of the rights hitherto enjoyed by the non-Jewish communities in Palestine.
organic fertilizers are highly variable in their nutritional compositions in terms of minerals and different organic and inorganic species. Even similar materials can differ significantly based on their source (e.g. the quality of manure varies based on an animal's diet). organic fertilizers are often sourced from animal byproducts, making disease transmission a serious concern for plants grown for human consumption or animal forage. organic fertilizers are often particulate, contain environmental pollutants, and can clog substrates or other growing equipment. Sieving or milling the organic materials to fine dusts is often necessary. biochemical degradation and conversion processes of complex organic materials can make their mineral ingredients available to plants. some organic materials (i.e. particularly manures and offal) can further degrade to emit foul odors under anaerobic conditions or emit nanoparticles. many organic molecules (i.e. sugars) demand additional oxygen during aerobic degradation, which is essential for cellular respiration in the plant roots. organic compounds (i.e. sugars, vitamins, a.o.) are not necessary for normal plant nutrition. Nevertheless, if precautions are taken, organic fertilizers can be used successfully in hydroponics.
Article 23 provided the possibility for other parts of Germany to join the Federal Republic (under the constitution of the Federal Republic of Germany). Article 146 provided the possibility for unification of all parts of Germany under a new constitution. After the peaceful revolution of 1989 in East Germany, the Volkskammer of the GDR on 23 August 1990 declared the accession of East Germany to the Federal Republic under Article 23 of the Basic Law and thus initiated the process of reunification, to come into effect on 3 October 1990. Nevertheless, the act of reunification itself (with its many specific terms and conditions; including fundamental amendments to the West German Basic Law) was achieved constitutionally by the subsequent Unification Treaty of 31 August 1990; that is through a binding agreement between the former GDR and the Federal Republic now recognising each another as separate sovereign states in international law. This treaty was then voted into effect on 20 September 1990 by both the Volkskammer and the Bundestag by the constitutionally required two-thirds majorities; effecting on the one hand, the extinction of the GDR and the re-establishment of Länder on the territory of East Germany; and on the other, the agreed amendments to the Basic Law of the Federal Republic. Amongst these amendments was the repeal of the very Article 23 in respect of which the GDR had nominally declared its postdated accession to the Federal Republic.
In 1971, New York Times reporter James Reston published an article on his acupuncture experiences in China, which led to more investigation of and support for acupuncture. The US President Richard Nixon visited China in 1972. During one part of the visit, the delegation was shown a patient undergoing major surgery while fully awake, ostensibly receiving acupuncture rather than anesthesia. Later it was found that the patients selected for the surgery had both a high pain tolerance and received heavy indoctrination before the operation; these demonstration cases were also frequently receiving morphine surreptitiously through an intravenous drip that observers were told contained only fluids and nutrients. One patient receiving open heart surgery while awake was ultimately found to have received a combination of three powerful sedatives as well as large injections of a local anesthetic into the wound. After the National Institute of Health expressed support for acupuncture for a limited number of conditions, adoption in the US grew further. In 1972 the first legal acupuncture center in the US was established in Washington DC and in 1973 the American Internal Revenue Service allowed acupuncture to be deducted as a medical expense. Ronald Reagan, as the governor of California, vetoed a law which decriminalized acupuncture. In 2006, a BBC documentary Alternative Medicine filmed a patient undergoing open heart surgery allegedly under acupuncture-induced anesthesia. It was later revealed that the patient had been given a cocktail of anesthetics.
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.
It is usually detected by LC-MS or HPLC-UV against a reference standard. In biological matrices, metabolite targeting can improve detection. No universal immunoassay is widely available.