circadian rhythm raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
This page was last updated on 2026-02-16 and is reviewed periodically as new material appears.
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.
SR9009 is not approved as a medicine by major regulatory agencies. It is commonly sold as a research chemical, a category that may fall outside customary drug approval and quality rules. In sports, the World Anti-Doping Agency lists SR9009 as a prohibited substance. Athletes who use it can face sanctions if it is detected in a sample. Legal status varies by country, and importation may be restricted. Enforcement practices differ across borders.
Detection of SR9009 in biological samples usually employs liquid chromatography coupled with tandem mass spectrometry. This method can identify the parent compound and sometimes metabolites in urine or blood. Because exposure can be low and clearance may be rapid, sample timing and limits of detection matter. Laboratories validate assays for sensitivity and specificity. Results are interpreted alongside chain-of-custody and quality-control records. Urine is the common matrix for anti-doping analysis, while blood may be used in research settings.
| 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. |
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.
Analytical identification and purity assessment often use high-performance liquid chromatography with ultraviolet detection or mass spectrometry. Liquid chromatography–tandem mass spectrometry is used to detect and quantify SR9009 in biological matrices, including urine and blood, for anti-doping or pharmacokinetic studies. Nuclear magnetic resonance spectroscopy can confirm molecular structure. Stability depends on form and storage: the solid is generally more stable than solutions, and repeated freeze–thaw cycles may degrade samples. Purity is typically reported as a percentage from a certificate of analysis.
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.
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.
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.
Cooling a mixture of iron with 0.8% carbon slowly below 723 °C to room temperature results in separate, alternating layers of cementite and α-iron, which is soft and malleable and is called pearlite for its appearance. Rapid cooling, on the other hand, does not allow time for this separation and creates hard and brittle martensite. The steel can then be tempered by reheating to a temperature in between, changing the proportions of pearlite and martensite. The end product below 0.8% carbon content is a pearlite-αFe mixture, and that above 0.8% carbon content is a pearlite-cementite mixture. In gray iron the carbon exists as separate, fine flakes of graphite, and also renders the material brittle due to the sharp edged flakes of graphite that produce stress concentration sites within the material. A newer variant of gray iron, referred to as ductile iron, is specially treated with trace amounts of magnesium to alter the shape of graphite to spheroids, or nodules, reducing the stress concentrations and vastly increasing the toughness and strength of the material. Wrought iron contains less than 0.25% carbon but large amounts of slag that give it a fibrous characteristic. Wrought iron is more corrosion resistant than steel. It has been almost completely replaced by mild steel, which corrodes more readily than wrought iron, but is cheaper and more widely available. Carbon steel contains 2.0% carbon or less, with small amounts of manganese, sulfur, phosphorus, and silicon.
In medicine, the urea-to-creatinine ratio (UCR), known in the United States as BUN-to-creatinine ratio, is the ratio of the blood levels of urea (BUN) (mmol/L) and creatinine (Cr) (μmol/L). BUN only reflects the nitrogen content of urea (MW 28), while urea measurement reflects the whole of the molecule (MW 60); urea is just over twice BUN (60/28 = 2.14). In the United States, both quantities are given in mg/dL. The ratio may be used to determine the cause of acute kidney injury or dehydration. The principle behind this ratio is the fact that both urea (BUN) and creatinine are freely filtered by the glomerulus; however, urea reabsorbed by the renal tubules can be regulated (increased or decreased) whereas creatinine reabsorption remains the same (minimal reabsorption).
M + Ph2CO → M+Ph2CO•− Generally sodium is used as the alkali metal. Sodium-benzophenone ketyl is used in the purification of organic solvents, particularly ethers, because it reacts with water and oxygen to give non-volatile products. Adsorbents such as alumina, silica gel, and especially molecular sieves are superior and far safer. The sodium-benzophenone method is common since it gives a visual indication that water, oxygen, and peroxides are absent from the solvent. Large scale purification may be more economical using devices which utilize adsorbents such as the aforementioned alumina or molecular sieves. The ketyl is soluble in the organic solvent being dried, which leads to faster purification. In comparison, sodium is insoluble, and its heterogeneous reaction is much slower. When excess alkali metal is present a second reduction may occur. The twice reduced specie presents as a clear red (extra-dry) solution. A color transformation from deep opaque blue (pure once-reduced benzophenone) to red with stages of opaque purple, indicate a mix of anion and bisanion.
Sources: en.wikipedia.org
== Prevalence == Approximately two-thirds of both INDs and new drug applications (NDAs) are small-molecule drugs. The rest is biopharmaceuticals. About half of the INDs fail in preclinical and clinical phases of drug development.
Nucleic acid analogues are compounds which are structurally analogous to naturally occurring RNA and DNA, through substitutions of any of its sugar, phosphate, and nucleobase components. They are used in medicine and in molecular biology research.
== Pharmacology == Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half-life of 20–179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam. Clorazepate exerts its pharmacological properties via increasing the opening frequency of the chloride ion channel of GABAA receptors. This effect of benzodiazepines requires the presence of the neurotransmitter GABA and results in enhanced inhibitory effects of the neurotransmitter GABA acting on GABAA receptors. Clorazepate, like other benzodiazepines, is widely distributed and is highly bound to plasma proteins; clorazepate also crosses readily over the placenta and into breast milk. Peak plasma levels of the active metabolite desmethyl-diazepam are seen between 30 minutes and 2 hours after oral administration of clorazepate. Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam.
Sources: en.wikipedia.org
The shells of green sea turtles and loggerhead sea turtles have been found in white shark stomachs in the Mediterranean, and bites have been recorded on leatherback sea turtles off central California. Around Seal Island, South Africa, white sharks are recorded to attack and kill seabirds like Cape cormorants, white-breasted cormorants, kelp gulls, Cape gannets, brown skuas, sooty shearwaters, and African penguins but rarely consume them.
=== Synthetic enzymes === Regardless of the details, an outstanding issue is that the physiological route of NAADP synthesis has still not been unequivocally identified — neither the reaction(s) nor the enzyme(s). Clearly, it is theoretically possible there may be multiple routes of synthesis, but this would be unprecedented in the second messenger world. To date, the most favoured hypothesis is the so-called base-exchange reaction (nicotinic acid + NADP → NAADP + nicotinamide; catalyzed by ADP-ribosyl cyclases) which are a family of enzymes that include CD38 and CD157 in mammals (and orthologs in sea urchin and Aplysia ovotestis). These were first discovered as the synthetic enzymes for cADPR but later revealed to be multifunctional, promiscuous enzymes that can also produce NAADP. Certainly NAADP production can occur in vitro but whether it occurs in vivo is another question (because genetic knockout or knock-down of ADP-ribosyl cyclases has no effect on NAADP production in some cell types), and there may be other routes which require different substrates and enzymes. The SARM1 enzyme also catalyzes the formation of NAADP from NAD+. The first chemical synthesis of NAADP was achieved in 2004 using a chemoenzymatic approach: a total chemical synthesis of NADP and then conversion of this to NAADP enzymatically.
It is a very specific tag that can be used for purification of membrane proteins. S-tag, a peptide derived from Ribonuclease A (KETAAAKFERQHMDS) SBP-tag, a peptide which binds to streptavidin (MDEKTTGWRGGHVVEGLAGELEQLRARLEHHPQGQREP) Softag 1, for mammalian expression (SLAELLNAGLGGS) Softag 3, for prokaryotic expression (TQDPSRVG) Spot-tag, a peptide recognized by a nanobody (PDRVRAVSHWSS) for immunoprecipitation, affinity purification, immunofluorescence and super resolution microscopy Strep-tag, a peptide which binds to streptavidin or the modified streptavidin called streptactin (Strep-tag II: WSHPQFEK) T7-tag, an epitope tag derived from the T7 major capsid protein of the T7 gene (MASMTGGQQMG). Used in different immunoassays as well as affinity purification Mainly used TC tag, a tetracysteine tag that is recognized by FlAsH and ReAsH biarsenical compounds (CCPGCC) Ty tag (EVHTNQDPLD) V5 tag, a peptide recognized by an antibody (GKPIPNPLLGLDST) VSV-tag, a peptide recognized by an antibody (YTDIEMNRLGK) Xpress tag (DLYDDDDK), a peptide recognized by an antibody
At a temperature below the boiling point, any matter in liquid form will evaporate until reaching equilibrium with the reverse process of condensation of its vapor. At this point the vapor will condense at the same rate as the liquid evaporates. Thus, a liquid cannot exist permanently if the evaporated liquid is continually removed. A liquid at or above its boiling point will normally boil, though superheating can prevent this in certain circumstances. At a temperature below the freezing point, a liquid will tend to crystallize, changing to its solid form. Unlike the transition to gas, there is no equilibrium at this transition under constant pressure, so unless supercooling occurs, the liquid will eventually completely crystallize. However, this is only true under constant pressure, so that (for example) water and ice in a closed, strong container might reach an equilibrium where both phases coexist. For the opposite transition from solid to liquid, see melting. The phase diagram explains why liquids do not exist in space or any other vacuum. Since the pressure is essentially zero (except on surfaces or interiors of planets and moons) water and other liquids exposed to space will either immediately boil or freeze depending on the temperature. In regions of space near the Earth, water will freeze if the sun is not shining directly on it and vaporize (sublime) as soon as it is in sunlight. If water exists as ice on the Moon, it can only exist in shadowed holes where the sun never shines and where the surrounding rock does not heat it up too much.
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.
Its legal status depends on the country and intended use. It is not an approved medicine in major jurisdictions. In sport, it is prohibited by anti-doping rules.