circadian clock raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
Reviewed 2026-02-01. Anything still debated is marked as such rather than presented as settled.
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.
Regulatory and sporting contexts treat SR9009 as a prohibited substance in many elite competitions. Its presence on banned lists reflects concerns about performance enhancement and unknown long-term safety. Analytical chemists have developed methods to detect the parent compound and its metabolites in urine and blood. Literature discussions distinguish between in vitro potency, animal pharmacology, and anecdotal human reports. The latter are difficult to verify because products sold online may lack purity or contain different compounds.
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.
Preclinical reports describe effects on exercise endurance, mitochondrial content, and lipid profiles in rodents, but these findings come from specific experimental conditions. Many studies use high doses or delivery methods that may not translate directly to human use. SR9009 has been reported to have low oral bioavailability and a short half-life, which complicates interpretation of oral dosing studies. It is not established as safe or effective for any indication. Literature discussions often separate its pharmacological mechanism from unverified claims made in fitness and supplement markets.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic REV-ERB agonist | Binds REV-ERBα and REV-ERBβ in preclinical models |
| Molecular formula | C20H24ClN3O4S | Reported for the parent compound |
| CAS Registry Number | 1379686-30-2 | Common identifier in chemical databases |
| Appearance | Off-white to pale yellow solid | Typical research chemical solid |
| Solubility | Soluble in DMSO and ethanol; low in water | Class: small organic molecule |
Most published work on SR9009 consists of preclinical studies. It is widely sold as a research chemical, a category that does not imply safety, efficacy, or pharmaceutical-grade quality. Sports anti-doping organizations have listed SR9009 as a prohibited substance, and its presence in an athlete sample can lead to sanctions. Legal status differs by country; in several jurisdictions it is not approved for human consumption and may be treated as an unapproved new drug.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is not a steroid, peptide, or natural hormone. In scientific literature, it appears under the code SR9009 and in non-scientific contexts as Stenabolic. The compound was identified through chemical screening efforts aimed at targeting circadian clock components. Its status remains investigational, and no regulatory agency has approved it as a human medicine.
REV-ERB proteins help regulate daily cycles in gene expression, including genes tied to lipid and glucose metabolism. SR9009 binds these receptors and alters their activity in cell and animal experiments. Consequences observed in rodents include changes in skeletal muscle oxidative capacity, blood lipid levels, and exercise performance. The precise chain from receptor occupancy to whole-body effects is still an active area of study. Human responses cannot be assumed from rodent data.
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.
Regulatory treatment of SR9009 varies by country and context. It is not approved as a therapeutic drug by agencies such as the United States Food and Drug Administration or the European Medicines Agency. Sports authorities list it as a prohibited substance; the World Anti-Doping Agency classifies it among hormone and metabolic modulators. Legal status for personal possession or sale differs across jurisdictions, and some countries may restrict it under analog or research chemical laws. Buyers who seek verified material often rely on independent laboratory testing because online product labels may not match contents.
Laboratory samples of SR9009 are typically handled as research chemicals rather than pharmaceuticals. Suppliers usually state that the material is for research use only and not for human or veterinary administration. Storage recommendations generally call for a freezer at approximately −20 °C, protection from light, and a desiccated environment. The solid is often described as a white to off-white powder. Solubility is commonly reported in organic solvents such as dimethyl sulfoxide and ethanol, with low solubility in water.
== Epidemiology == Tendon injury and resulting tendinopathy are responsible for up to 30% of consultations to sports doctors and other musculoskeletal health providers. Tendinopathy is most often seen in tendons of athletes either before or after an injury but is becoming more common in non-athletes and sedentary populations. For example, the majority of patients with Achilles tendinopathy in a general population-based study did not associate their condition with a sporting activity. In another study the population incidence of Achilles tendinopathy increased sixfold from 1979–1986 to 1987–1994. The incidence of rotator cuff tendinopathy ranges from 0.3% to 5.5% and annual prevalence from 0.5% to 7.4%.
For the Kharaa (alien) side, winning requires destroying all marine "Infantry Portals", ensuring that they do not respawn, and then eliminating the rest of the marines. Other possibilities exist such as destroying the command chair, or destroying all finished hives, and killing the whole alien team before the remaining hive is fully grown. Game duration and game balance has been continually addressed by Unknown Worlds Entertainment throughout each of their releases with extensive changelogs describing these issues. In v1, games were slower and often measured in hours. One of the stated aims of v2 was to address this, by introducing a broad range of changes to abilities, structures, etc. In current releases (v3), a typical game lasts 5–15 minutes, but can run over an hour, with both sides vying for control over strategically important Hive Rooms and Resource Nodes. Combat is the team deathmatch, or beginner mode of NS. It was introduced in NS 3.0 to help new players learn how to play alien lifeforms in an easier environment. Neither team can build structures, the marines do not have a commander, and aliens have only one hive. Each player has an individual experience meter, increased by killing enemies; dealing damage to the enemy hive/command chair or healing/repairing their own hive/command chair. When the experience meter reaches maximum, the player gains a level and it resets.
=== Nymphs === It is often difficult to distinguish Eupolyphaga species by their nymphs. Nymphs are generally similar in appearance to females, being reddish brown to dark brown in color, though lighter variations are possible. They will appear white in color prior to sclerotization. While common throughout the genus, sex of individuals can be determined in the last nymphal instar, largely due to their sexual dimorphism at maturity. Male nymphs have four distinct wing buds, while the females have none.
Liu Wenhui travelled to Chongqing to negotiate with Liu Xiang, but Liu Xiang would not hand over the confiscated shipment. This was because Liu Xiang had a policy of not allowing any other Sichuanese warlord to gain aircraft (he himself had already acquired a rudimentary air force consisting of several Potez 25 and Breguet 14 bombers). Western sources also agree that Liu Wenhui tried obtaining aircraft, although according to them the aircraft were either seized in Hankou by the central government or crashed en route to Chengdu. The Chinese sources go further by asserting that in May 1931, Liu Wenhui attempted to bribe Liu Xiang's subordinates, including Fan Shaozhen, to join him, but they reported this matter to Liu Xiang, causing Liu to waste 450,000 yuan. An angered Liu supposedly then cut off Liu Xiang's grain supply, forcing the Chongqing warlord to urgently purchase grain from Hunan to prevent hunger. Whatever the matter, it is clear that Liu Wenhui's once-cooperative relationship with his nephew, General Liu Xiang, had soured and turned into a rivalry. On 19 October 1932, Liu Xiang's general, Tang Shizun, and ninety-four other Sichuanese warlords issued a circular telegram to denounce Liu Wenhui. The telegram asserted that Liu was power-hungry, unscrupulous, corrupt, and nepotistic, with no real plans for governing Sichuan and resorting to underhanded tactics such as bribery, backstabbing, and banditry to gain and maintain power. On the eve of war in 1932, Liu Wenhui's armies were estimated at around 120,000 men, slightly outnumbering Liu Xiang's 100,000.
Sources: en.wikipedia.org
BioDuro is an American contract research, development, and manufacturing organization (CRDMO) headquartered in Irvine, California. Founded in 1996, the company operates seven R&D and manufacturing campuses across the United States and China and employs more than 2,000 scientists worldwide. BioDuro provides integrated services from discovery through commercial manufacturing, including medicinal chemistry, biology, drug metabolism and pharmacokinetics (DMPK), drug substance, and drug product development. Its capabilities extend across modalities such as small molecules, peptides, oligonucleotides, and antibody–drug conjugates (ADCs).
== Side effects == Possible side effects of olanzapine/fluoxetine include all those of the two component drugs: olanzapine (side effects) and fluoxetine (side effects). Common side effects include suicidal thoughts, increased appetite, weight gain, drowsiness, fatigue, dry mouth, swelling, tremor, blurred vision, and difficulty concentrating. Olanzapine/fluoxetine could produce a severe allergic reaction and should not be used if the patient has previously experienced an allergic reaction to either fluoxetine or olanzapine. Olanzapine is correlated with an increase in blood sugar. Patients with diabetes, or those at risk for developing it, require careful monitoring. In rare cases, olanzapine/fluoxetine may cause neuroleptic malignant syndrome. Like other SSRIs, olanzapine/fluoxetine carries a boxed warning stating that it could increase the risk of suicidal thoughts and behaviors in patients aged 24 and under. The warning also states that olanzapine/fluoxetine may increase the risk of death in elderly patients with dementia-related psychosis.
25 May – Deputy Prime Minister Angela Rayner refuses to confirm whether the government will remove the two-child benefit cap in the 2025 budget. Nigel Farage says that Reform UK would scrap the two-child benefit cap, and restore winter fuel payments to pensioners, if elected. Labour's renationalisation of the UK's railways begins as the train operator South Western Railway is taken into public ownership. 26 May – King Charles III and Queen Camilla begin a two day visit to Canada, where the King will deliver a Speech from the throne in the Canadian Parliament, the first such speech in the country for 50 years. 27 May – Charles III addresses the opening session of the 45th Canadian Parliament, and receives a standing ovation from Canadian MPs following a speech in support of Canada staying "strong and free". Nigel Farage says that a future Reform UK government would introduce generous tax breaks for married couples to make it easier for them to have children, and scrap the two-child benefit cap. 29 May – The UK government reveals its plans for overhauling pension investment funds to create models similar to those in Australia and Canada; the plans include the creation of £25bn "megafunds" which will be instructed to make a portion of their investments locally to help fuel economic growth. In a speech attacking Reform policy, Starmer accuses Farage of "fantasy economics" and says his unfunded tax cuts would "crash the economy" like Liz Truss.
Singapore's public transport network is shaped up with trains (consisting of the MRT and LRT systems), buses and taxis. There are currently six MRT lines (North–South Line, East–West Line, North East Line, Circle Line, Downtown Line and Thomson–East Coast Line), three LRT lines serving the neighbourhoods of Bukit Panjang and Choa Chu Kang (Bukit Panjang LRT line), Sengkang (Sengkang LRT line) and Punggol (Punggol LRT line), covering around 241 km (150 mi) in total, and more than 300 bus routes in operation. Taxis are a popular form of transport as the fares are relatively affordable when compared to many other developed countries, whilst cars in Singapore are the most expensive to own worldwide. Singapore has a road system covering 3,356 kilometres (2,085 mi), which includes 161 kilometres (100 mi) of expressways. The Singapore Area Licensing Scheme, implemented in 1975, became the world's first congestion pricing scheme, and included other complementary measures such as stringent car ownership quotas and improvements in mass transit. Upgraded in 1998 and renamed Electronic Road Pricing (ERP), the system introduced electronic toll collection, electronic detection, and video surveillance technology. A satellite-based system was due to replace the physical gantries by 2020, but has been delayed until 2026 due to global shortages in the supply of semiconductors. As Singapore is a small island with a high population density, the number of private cars on the road is restricted with a pre-set car population quota, to curb pollution and congestion.
NONMEM is a non-linear mixed-effects modeling software package developed by Stuart L. Beal and Lewis B. Sheiner in the late 1970s at University of California, San Francisco, and expanded by Robert Bauer at Icon PLC. Its name is an acronym for nonlinear mixed effects modeling but it is especially powerful in the context of population pharmacokinetics, pharmacometrics, and PK/PD models. NONMEM models are written in NMTRAN, a dedicated model specification language that is translated into FORTRAN, compiled on the fly and executed by a command-line script. Results are presented as text output files including tables. There are multiple interfaces to assist modelers with housekeeping of files, tracking of model development, goodness-of-fit evaluations and graphical output, such as PsN and xpose and Wings for NONMEM. Current version for NONMEM is 7.5.
Sources: en.wikipedia.org
==== Omega-6:omega-3 ratio ==== A 2024 review stated that dietary recommendations should not be made based on the omega-6:omega-3 ratio, but rather on their absolute dietary intake levels. The omega-6:omega-3 ratio is calculated by accounting for all of the omega-6 fatty acids in the diet or blood divided by the sum of all omega-3 fatty acids. Concern about a high omega-6:omega-3 ratio was based on the competition between linoleic acid and alpha-linolenic acid for desaturation enzymes, and because metabolites of omega-6 fatty acids were considered to be pro-inflammatory. However, there is insufficient evidence in humans that omega-6 fats are pro-inflammatory and that omega-3 fats are anti-inflammatory. In contrast, higher omega-6 levels are associated with lower inflammatory status, indicating that intake of omega-6 fats is not a dietary concern, and that relatively low intake of dietary omega-3 fats may lead to inflammation. Accordingly, use of the omega-6:omega-3 ratio has been rejected as an inflammation biomarker by health agencies worldwide. Numerous health and scientific organizations recommend intake of omega-6 seed oils as part of a healthy diet to replace sources of saturated fats, such as in palm and coconut oils, butter, tallow, and lard.
The Greek key motif consists of four adjacent antiparallel strands and their linking loops. It consists of three antiparallel strands connected by hairpins, while the fourth is adjacent to the first and linked to the third by a longer loop. This type of structure forms easily during the protein folding process. It was named after a pattern common to Greek ornamental artwork (see meander). Due to the chirality of their component amino acids, all strands exhibit right-handed twist evident in most higher-order β-sheet structures. In particular, the linking loop between two parallel strands almost always has a right-handed crossover chirality, which is strongly favored by the inherent twist of the sheet. This linking loop frequently contains a helical region, in which case it is called a β-α-β motif. A closely related motif called a β-α-β-α motif forms the basic component of the most commonly observed protein tertiary structure, the TIM barrel.
Preparing TNP-ATP is a one-step synthesis that is relatively safe and easy. Adenosine's ribose moiety can be trinitrophenylated by 2,4,6-trinitrobenzene-1-sulfonate (TNBS). The resulting compound assumes a bright orange color and has visible absorption characteristics, as is characteristic of a Meiseinheimer spiro complex compound linking. To see the exact method of preparion, please refer to T. Hiratsuka's and K. Uchida's paper "Preparation and Properties of 2'(r 3')-O(2,4,6-trinitrophenyl) Adenosine 5'-triphosphate, an Analog of Adenosine Triphosphate," found in the reference section. To revert TNP-ATP back to its constituent parts, or in other words to hydrolyze TNP-ATP to give equilmolar amounts of picric acid (TNP) and ATP, TNP-ATP should be treated with 1 M HCl at 100 degrees Celsius for 1.5 hours. This is because if TNP-ATP is acidified under mild conditions, it results in the opening of the dioxolane ring attached to the 2’-oxygen, leaving a 3’O-TNP derivative as the only product.
AM concentrations are substantially elevated during intense inflammation from disorders like sepsis, rendering AM a potentially viable therapeutic agent and clinical mode of monitoring such inflammation. AM contributes to vasodilation, which could be detrimental in leading to septic shock. Researchers seek to mitigate this effect while maintaining ADM's antimicrobial, anti-inflammatory, and endothelial-protective characteristics by employing antibodies that bind to ADM's N-terminus or co-administering ADM with ADM-binding protein-1, which collectively extend ADM's half-life and increase its maintenance role while minimizing this detrimental vasodilation. While AM has been discussed in regard to its implications for bacterial infections, such as sepsis, prior research explores its potential connection to viral infections too. This annunciates the importance of continual investigation into AM's mechanisms with viral illnesses through exploring its roles in inflammation and immune regulation.
Sources: en.wikipedia.org
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.
No. It is a synthetic ligand that binds nuclear receptors, not a steroid or peptide hormone. Its activity depends on receptor binding rather than endocrine secretion.
Clinical evidence is limited. Most published data come from cell and animal experiments. Human safety and efficacy remain uncertain.
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.