This is a working overview of circadian clock, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-08-01. Anything still debated is marked as such rather than presented as settled.
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.
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.
| 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. |
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.
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.
Laboratory identification of SR9009 typically relies on chromatographic separation coupled to mass spectrometry, often with ultraviolet detection as a secondary check. Nuclear magnetic resonance spectroscopy can confirm molecular structure when a reference standard is available. Because many suppliers sell the compound as a research chemical, independent identity testing is important for experimental reproducibility. A single retention time is not sufficient proof of identity, especially when related compounds may be present. Purity assessments usually report a percentage based on area normalization.
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.
Johann Eduard Hari (born 21 January 1979) is a British writer and journalist. Until 2011, Hari wrote for The Independent, among other outlets, before resigning after admitting to plagiarism and fabrications dating back to 2001 and making malicious edits to the Wikipedia pages of journalists who had criticised his conduct. He has since written books on the topics of depression, the war on drugs, the effect of technology on attention span, and anti-obesity medication.
== Relevance to human disease == Neuropeptides such as relaxin-3 are attracting increasing interest as targets for the pharmacological treatment of a range of neuropsychiatric diseases. Due to the ability of relaxin-3 to modulate neuronal processes/behaviours such as mood, stress responses and cognition, which are often aberrant in mental illnesses, considerable potential exists for the development of relaxin-3-based drugs to therapeutically treat depression and other mental illnesses.
The UK government announces that legislation will be brought forward to ban sex offenders in England and Wales from changing their names to avoid detection. 10 May The UK economy is reported to have moved out of recession, with 0.6% growth between January and March, the fastest rate for two years. 75-year-old Piran Ditta Khan is sentenced to life imprisonment, with a minimum term of 40 years, for the shooting dead of police officer Sharon Beshenivsky during an armed robbery in 2005. Two elderly women from climate protest group Just Stop Oil target Magna Carta in the British Library, attempting to smash its glass container with a hammer and chisel. The documents themselves are undamaged. The Liberty, a device that allows cancer patients to take some blood tests at home and upload the data, is given approval for use at 12 cancer treatment sites within the NHS. The Co-op Live arena says it is ready to open after completing safety checks, with Elbow scheduled to perform as the opening act on 14 May. 11 May – The hottest day of the year so far is recorded by the Met Office, with temperatures peaking at 25.9 °C (78.6 °F) in Herstmonceux, East Sussex. 12 May Foreign Secretary David Cameron tells the BBC's Sunday with Laura Kuenssberg that a ban on the sale of UK weapons to Israel would only strengthen Hamas. Yellow weather warnings are in place for heavy rain and flooding as the brief hot spell comes to an end. 13 May The first new Royal Warrant Holders are issued by King Charles III and Queen Camilla.
Sources: en.wikipedia.org
==== Role of inhibitory neuron classes ==== The Sur lab pioneered two-photon measurements of neuronal activity in the intact mouse brain with cell-specific manipulations of activity to discover specific and unique functions of inhibitory neuron classes in cortical responses. Probing neuromodulator-dependent mechanisms of internal states, they demonstrated that cholinergic inputs to inhibitory neuron classes shape the temporal dynamics of cortical activity, including neuronal desynchronization during arousal and attention. Role of norepinephrine in cortical circuits and learning The Sur lab showed that control of norepinephrine release by locus coeruleus neurons via local GABAergic neurons strongly influences arousal, and phasic norepinephrine activity signals uncertainty and reward prediction to modulate task execution and reinforcement learning during goal-directed behavior. Together, these discoveries have shaped the understanding that specific excitatory and inhibitory cortical circuits mediate unique functions, and neuromodulator systems act via cell-specific circuits to modulate cortical functions, brain states and learning.
The photosynthetic partners, or photobionts, of X. parietina belong to the green algal genus Trebouxia, including Trebouxia arboricola and T. irregularis. These algae also exist independently in nature, occurring on both lichen-colonized and lichen-free bark. A study found that the photobiont occupies 7% of the thallus volume in X. parietina. Pigmentation density in the upper cortex varies, regulating light exposure to the algae. The Trebouxia photobiont adjusts its photosynthetic activity seasonally, supporting X. parietina in sunlit environments. As sunlight increases in spring, the photobiont reduces chlorophyll levels and produces protective pigments to dissipate excess light as heat. Chlorophyll concentrations are lowest in spring and peak in winter, balancing light absorption and photoprotection throughout the year. X. parietina associates with diverse photobionts. It primarily partners with Trebouxia decolorans when growing on bark and with T. arboricola on rock. Even within local populations, genetically distinct photobionts often coexist in adjacent thalli. One study identified 36 algal genotypes among 38 epiphytic samples from a single site. Despite T. decolorans being assumed to reproduce asexually, multiple algal strains sometimes occur within a single thallus, suggesting photobiont switching or thallus fusion. This diversity may contribute to X. parietina's adaptability across varied environments. Although free-living algae are abundant, X. parietina selectively associates with Trebouxia species.
==== Eye tissue ==== Damage to the cornea causes significant vision impairment, the most common treatment for which is allograft cornea transplantation. However, donor corneal grafts are in short supply and, like other tissue grafts, carry the risk of rejection or communicable disease. Thus, tissue engineered options are desirable. In silk biomaterial scaffolds which replicate the hierarchical structure of the cornea, the addition of RGD improved cell attachment, alignment, proliferation, and ECM protein expression. Additionally, RGD has been used in regeneration of retinal pigmented epithelium. This tissue can be generated from human embryonic and induced pluripotent stem cells, however with inefficient differentiation. It has been shown that RGD-alginate hydrogels improve derivation of retinal tissue from stem cells.
The history of the group now known as Socialist Studies dates to 1991, when the Camden and North West London branches were expelled from the SPGB in a party-wide referendum. Some of these ex members, comprising sixteen individuals, refused to recognise the expulsions and attempted to continue operating as the SPGB, which they claimed to have "reconstituted". Among them were Edgar Hardcastle and Cyril May, who became their central organiser. As the original SPGB had never been dissolved and indeed continued to operate following the expulsions, it successfully mounted various legal challenges against Socialist Studies's use of the SPGB name. Because of this and to differentiate itself from the original SPGB, the group has variously referred to itself in its publicity material as the Reconstituted Socialist Party of Great Britain, the New Socialist Party of Great Britain and Socialist Studies. Third parties refer to them as the Socialist Studies group. The group's activity consists primarily of publishing Socialist Studies and various pamphlets and holding occasional propaganda meetings. Socialist Studies was not a registered political party until December 2006, when they registered with the Electoral Commission as Socialist Studies Party (1904). As of 2015, they have never contested a local, national, or European Union election.
Sources: en.wikipedia.org
The global annual production of freshwater prawns (excluding crayfish and crabs) in 2007 was about 460,000 tonnes, exceeding 1.86 billion dollars. Additionally, China produced about 370,000 tonnes of Chinese river crab. In addition astaciculture is the freshwater farming of crayfish (mostly in the US, Australia, and Europe).
At the Battle of Leipzig in Saxony (16–19 October 1813), also called the "Battle of the Nations", 191,000 French fought more than 300,000 Allies, and the defeated French had to retreat into France. After the French withdrawal from Germany, Napoleon's remaining ally, Denmark–Norway, became isolated and fell to the coalition.
Each coordinated water molecule may be attached by hydrogen bonds to other water molecules. The latter are said to reside in the second coordination sphere. However, for the alkali metal cations, the second coordination sphere is not well-defined as the +1 charge on the cation is not high enough to polarise the water molecules in the primary solvation shell enough for them to form strong hydrogen bonds with those in the second coordination sphere, producing a more stable entity. The solvation number for Li+ has been experimentally determined to be 4, forming the tetrahedral [Li(H2O)4]+: while solvation numbers of 3 to 6 have been found for lithium aqua ions, solvation numbers less than 4 may be the result of the formation of contact ion pairs, and the higher solvation numbers may be interpreted in terms of water molecules that approach [Li(H2O)4]+ through a face of the tetrahedron, though molecular dynamic simulations may indicate the existence of an octahedral hexaaqua ion. There are also probably six water molecules in the primary solvation sphere of the sodium ion, forming the octahedral [Na(H2O)6]+ ion. While it was previously thought that the heavier alkali metals also formed octahedral hexaaqua ions, it has since been found that potassium and rubidium probably form the [K(H2O)8]+ and [Rb(H2O)8]+ ions, which have the square antiprismatic structure, and that caesium forms the 12-coordinate [Cs(H2O)12]+ ion.
Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex. It is no longer available in the UK (since 2018), however is available in other countries as a prescription-only drug.
== Clinical trials == The drug was reported to improve motivation and reduce apathy in people with Parkinson's disease in a phase 2a clinical trial. As of September 2024, pirepemat is in phase 2 clinical trials for Parkinson's disease. A phase 3 trial is being planned. The drug was also under development for the treatment of "behavioral disorders" and attention deficit hyperactivity disorder (ADHD). However, no recent development for the former indication has been reported and development for ADHD was discontinued. In August 2020, pirepemat received an INNTooltip International Nonproprietary Name with a novel suffix reflecting its reputedly new and unique mechanism of action. Pirepemat is under development by Integrative Research Laboratories (IRLAB).
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 research compound that activates the REV-ERBα and REV-ERBβ nuclear receptors. It is not an approved drug and has no established human therapeutic use. Most published biological data come from cell and rodent studies.