If you have been reading about circadian clock and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2026-05-25. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common name | SR9009 | Also referred to as Stenabolic in non-scientific contexts. |
| Chemical class | Synthetic small molecule | Not a steroid or peptide hormone. |
| Receptor target | REV-ERBα and REV-ERBβ | Nuclear receptor agonist in preclinical studies. |
| Development status | Investigational | No approved human therapeutic indication. |
| Regulatory attention | Prohibited in sport | Listed by anti-doping authorities. |
Several misconceptions surround SR9009. It is often described as a SARM, a steroid, or an exercise pill, but its known target is the REV-ERB receptor family. Rodent studies have examined exercise capacity and metabolic markers, yet human outcomes remain unproven. Oral bioavailability appears low in animals, and human pharmacokinetics are not well characterized. Online products may contain impurities or different compounds, so identity and purity testing are important for research use.
Analytical chemists detect SR9009 with liquid chromatography-tandem mass spectrometry, commonly abbreviated LC-MS/MS. Sample preparation may involve protein precipitation, liquid-liquid extraction, or solid-phase extraction before analysis. Laboratories can target the parent compound or its metabolites, depending on the matrix and the purpose of testing. Anti-doping methods require sensitive and specific assays because concentrations in biological samples can be low. Reference standards and validated methods are essential for reliable identification and quantification.
For chemical elements without isolated molecules, such as carbon and metals, the molar mass is calculated using the relative atomic mass of the element, usually given by the standard atomic weight indicated in the periodic table. Thus, for example, the molar mass of iron is about 55.845 g/mol.
=== Lisa Dearn === Lisa Dearn (Chloe Pirrie) is the deputy energy secretary leading the government inquest against Lumi following its collapse. She presses Robert and Henry with pointed questions about Pierpoint's overvaluation of Lumi, as well as Henry's sexual harassment of his employees. In series 4, Lisa is now Secretary of State for Business and Trade. Her far-left views trouble Lord Norton, who is concerned about the waning influence of legacy media under the new Labour government, and perceives her stance as anti-business. She and Minister for Industry Jennifer Bevan meet with Henry, now CEO of payment processing startup Tender, and CFO Whitney Halberstram, when the two seek regulatory approval for a merger with IBN Bauer Bank. Lisa is skeptical of the merger, deeming it monopolistic and self-serving on Henry's part, but the Prime Minister's chief of staff Ricky Martyn arrives to pressure the regulator into approving the merger lest Labour appear anti-business, with Bevan implied to have engineered the intervention. Government support for Tender forces Lisa to publicly back the company as beneficial to the UK consumer during the launch of its banking app, despite her personal skepticism and disgust for Henry. After news breaks of Tender's fraud, Yasmin plots to pin the company's failure on the Labour government, and circulates a lie in the press that Dearn suppressed an internal memo voicing concerns about Tender while expediting Tender's banking license and regulatory approvals.
== Early life and education == Shawn was born in New York City to a Jewish family. His parents were journalist Cecille (née Lyon) and William Shawn, the longtime editor of The New Yorker. He has younger twin siblings: composer Allen Shawn, and Mary, who is autistic and lives in an institution. William was the son of emigrants from Central Europe. Shawn grew up on Manhattan's Upper East Side. He attended The Collegiate School on Manhattan's West Side before transferring to The Putney School, a private liberal arts high school in Putney, Vermont. After high school, he studied history at Harvard University, graduating in 1965 with a Bachelor of Arts. He then studied philosophy, politics and economics, as well as Latin, at Magdalen College, Oxford, originally intending to become a diplomat. He traveled to India as an English teacher on a Fulbright program.
Arizona reports its first death of the Sin Nombre strain of hantavirus pulmonary syndrome. Actor James Handy is killed in his Los Angeles home following a fatal stabbing wound. The son of Handy's girlfriend is later arrested. Gallup releases a poll saying support for same-sex marriage in the U.S. has declined after two decades of growth, with 65% of adults saying it should be legal, down from 71% in 2022 and 2023. June 4 The Kennedy Center orders staff to remove all references to Donald Trump's name from the building following a court ruling. Arizona Attorney General Kris Mayes says she will seek new indictments against fake electors involved in attempting to overturn the 2020 election in the state following a denial of an appeal by Mayes that would require prosecutors to send the case back to the grand jury. The U.S. House passes legislation to provide new aid to Ukraine and new sanctions on Russia. ICE ends a Biden-era policy to report detainee deaths that occur within 30 days of leaving custody. June 5 Federal judge John McConnell Jr. strikes down the Trump administration’s policy that halted asylum and green card proceedings for applicants from 39 countries. The ruling states ICE's actions are arbitrary and capricious and ignore the law. The National Football League's Chicago Bears vote to advance plans for stadium development in Hammond in northwest Indiana to replace Soldier Field as its home stadium. However, the site of the stadium still remains determined. The FDA says that Target has recalled two types of baby wipes due to bacterial contamination.
1H (atomic mass 1.007825031898(14) Da) is the most common hydrogen isotope, with an abundance of > 99.98%. Its nucleus consists of only a single proton, so it has the formal name protium. The proton has never been observed to decay, so 1H is considered stable. It is the only stable nuclide with no neutrons. Some Grand Unified Theories proposed in the 1970s predict that proton decay can occur with a half-life between 1028 and 1036 years. If so, then 1H (and all nuclei now believed to be stable) are only observationally stable. As of 2018, experiments have shown that the mean lifetime of the proton is > 3.6×1029 years.
Sources: en.wikipedia.org
== Chemistry == Metformin hydrochloride (1,1-dimethylbiguanide hydrochloride) is freely soluble in water, slightly soluble in ethanol, but almost insoluble in acetone, ether, or chloroform. The pKa of metformin is 12.4. The usual synthesis of metformin, originally described in 1922, involves the one-pot reaction of a heated solution of dimethylamine hydrochloride and 2-cyanoguanidine.
Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux. Pepsin remains in the larynx (pH 6.8) following a gastric reflux event. While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events. Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage. Pepsin may also cause mucosal damage during weakly acidic or non-acid gastric reflux. Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury. Under non-acid conditions (neutral pH), pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by a process known as receptor-mediated endocytosis. The receptor by which pepsin is endocytosed is currently unknown. Upon cellular uptake, pepsin is stored in intracellular vesicles of low pH at which its enzymatic activity would be restored. Pepsin is retained within the cell for up to 24 hours. Such exposure to pepsin at neutral pH and endocyctosis of pepsin causes changes in gene expression associated with inflammation, which underlies signs and symptoms of reflux, and tumor progression. This and other research implicates pepsin in carcinogenesis attributed to gastric reflux. Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux.
Germany Several P-51s were captured by the Luftwaffe as Beuteflugzeug ("captured aircraft") following crash landings. These aircraft were subsequently repaired and test-flown by the Zirkus Rosarius, or Rosarius Staffel, the official Erprobungskommando of the Luftwaffe High Command, for combat evaluation at Göttingen. The aircraft were repainted with German markings and bright yellow noses, tails, and bellies for identification. P-51B/P-51Cs – including examples marked with Luftwaffe Geschwaderkennung codes T9+CK, T9+FK, T9+HK, and T9+PK (with the "T9" prefix not known to be officially assigned to any existing Luftwaffe formation from their own records, outside of the photos of Zirkus Rosarius–flown aircraft)—with a total of three captured P-51Ds were also flown by the unit. Some of these P-51s were found by Allied forces at the end of the war; others crashed during testing. The Mustang is also listed in the appendix to the novel KG 200 as having been flown by the German secret operations unit KG 200, which tested, evaluated, and sometimes clandestinely operated captured enemy aircraft during World War II. Guatemala
The number of sponsored research centers grew to 14 during PSI-2. Four centers were selected as Large Scale centers, with a mandate to place 15% effort on targets nominated by the broader research community, 15% on targets of biomedical relevance, and 70% on broad structural coverage; these centers were the Joint Center for Structural Genomics (JCSG), the Midwest Center for Structural Genomics (MCSG), the Northeast Structural Genomics Consortium (NESG), and the New York SGX Research Center for Structural Genomics (NYSGXRC). The new centers participating in PSI-2 included four specialized centers: Accelerated Technologies Center for Gene to 3D Structure (ATCG3D), the Center for Eukaryotic Structural Genomics (CESG), the Center for High-Throughput Structural Biology (CHTSB), a branch of the Structural Genomics of Pathogenic Protozoa Consortium taking that institution's place), the Center for Structures of Membrane Proteins (CSMP), and the New York Consortium on Membrane Protein Structure (NYCOMPS). Two homology modeling centers, the Joint Center for Molecular Modeling (JCMM) and New Methods for High-Resolution Comparative Modeling (NMHRCM) were also added, as well as two resource centers, the PSI Materials Repository (PSI-MR) and the PSI Structural Biology Knowledgebase (SBKB). The TB Structural Genomics Consortium was removed from the roster of supported research centers in the transition from PSI-1 to PSI-2.
=== Pseudohyperkalemia === Pseudohyperkalemia occurs when the measured potassium level is falsely elevated. Mechanical trauma during blood drawing can cause potassium leakage out of the red blood cells due to haemolysis of the blood sample. Fist clenching during the blood draw can cause a rise in potassium levels in the venous blood as it is sampled; this difference may be as much as 1 mmol/L. Differences of this order of magnitude cause problems (false positive results for clinically-important hyperkalemia) for patients with low glomerular filtration rate (GFR; a measure of kidney function), type IV renal tubular acidosis (RTA), or on evidence-based medication for cardio-renal risk (RASi, MRAs). The practice, widespread in laboratories in North America, should be discontinued. Prolonged storage of blood samples or agitation in transit is also associated with red cell lysis that can increase serum potassium levels. Hyperkalemia may become apparent when a person's platelet concentration is more than 500,000/microL in a clotted blood sample (serum blood sample). Potassium leaks out of platelets after clotting has occurred. A high white cell count (greater than 120,000/microL) in people with chronic lymphocytic leukemia increases the fragility of red blood cells, thus causing pseudohyperkalemia during blood processing. This problem can be avoided by processing serum samples, because clot formation protects the cells from haemolysis during processing.
Sources: en.wikipedia.org
Until the late 1950s, the Precambrian was not believed to have hosted multicellular organisms. However, with radiometric dating techniques, it has been found that fossils initially found in the Ediacara Hills in Southern Australia date back to the late Precambrian. These fossils are body impressions of organisms shaped like disks, fronds and some with ribbon patterns that were most likely tentacles. These are the earliest multicellular organisms in Earth's history, despite the fact that unicellularity had been around for a long time before that. The requirements for multicellularity were embedded in the genes of some of these cells, specifically choanoflagellates. These are thought to be the precursors for all animals. They are highly related to sponges (Porifera), which are the simplest multicellular animals. In order to understand the transition to multicellularity during the Precambrian, it is important to look at the requirements for multicellularity—both biological and environmental.
Several complications can occur as a result of sCSFLS including decreased cranial pressure, brain herniation, infection, blood pressure problems, transient paralysis, and coma. The primary and most serious complication of a spontaneous cerebrospinal fluid leak is spontaneous intracranial hypotension, where pressure in the brain is severely decreased. This complication leads to the hallmark symptom of severe orthostatic headaches. People with cranial CSF leaks, the rarer form, have a 10% risk of developing meningitis per year. If cranial leaks last more than seven days, the chances of developing meningitis are significantly higher. Spinal CSF leaks cannot result in meningitis due to the sterile conditions of the leak site. When a CSF leak occurs at the temporal bone, surgery becomes necessary in order to prevent infection and repair the leak. Orthostatic hypotension is another complication that occurs due to autonomic dysfunction when blood pressure drops significantly. The autonomic dysfunction is caused by compression of the brainstem, which controls breathing and circulation. Low CSF volume can cause the cerebellar tonsil position to descend, which can be mistaken for Chiari malformation; however when the CSF leak is repaired the tonsil position often returns to normal (as seen in upright MRI) in this "pseudo-Chiari" condition. A further, albeit rare, complication of CSF leak is transient quadriplegia due to a sudden and significant loss of CSF. This loss results in hindbrain herniation and causes major compression of the upper cervical spinal cord.
== Veterinary medicine == Tramadol was the most common opioid prescribed by American veterinarians from 2014 to 2019; however, usage has declined in subsequent years due to more recent evidence suggesting that dogs do not metabolise tramadol into O-desmethyltramadol effectively. As metabolisation of tramadol relies on cytochrome P450 enzymes, it is species dependent and even individual genetics can have a profound impact on the efficacy of tramadol. A 2021 meta-analysis of tramadol use in dogs found that although tramadol was more effective than nalbuphine and codeine, it was less effective than methadone, COX inhibitors and multimodal analgesia with poor evidence to support the use of it is an analgesic for dogs. The mean alveolar concentration sparing effect of tramadol is negligible and with a high likelihood of rescue analgesia being required thus tramadol monotherapy is not recommended for the dog. One study looking at tramadol and meloxicam administered preoperatively provided no benefit compared to meloxicam given alone. Another study looking at cimicoxib versus tramadol for long-term post-operative pain following a tibial-plateau-levelling osteotomy found that although the level of analgesia was similar cimicoxib resulted in better mobility and a lower incidence of hock oedema. These studies and other evidence suggest that non-steroidal anti-inflammatory drugs provide superior analgesia to tramadol in dogs. Tramadol is more effective in cats although oral tramadol is poorly tolerated leading to low compliance.
18 March to 28 February 1971 The 198th Light Infantry Brigade and ARVN 6th Regiment, 2nd Division launch Operation Geneva Park to pacify Quảng Ngãi Province. the operation results in 2,337 PAVN killed and 67 captured, U.S. losses are 231 killed.
=== Laboratory testing === Because newborn screening programs test for a number of conditions, a number of laboratorial methodologies are used, as well as bedside testing for hearing loss using evoked auditory potentials and congenital heart defects using pulse oximetry. In the early 1960s Newborn screening started out using simple bacterial inhibition assays to screen for a single disorder, starting with phenylketonuria. With this testing methodology, newborn screening required one test to detect one condition. As mass spectrometry became more widely available, the technology allowed rapid determination of a number of acylcarnitines and amino acids from a single dried blood spot. This increased the number of conditions that could be detected by newborn screening. Enzyme assays are used to screen for galactosemia and biotinidase deficiency. Immunoassays measure thyroid hormones for the diagnosis of congenital hypothyroidism and 17α-hydroxyprogesterone for the diagnosis of congenital adrenal hyperplasia. Molecular techniques are used for the diagnosis of cystic fibrosis and severe combined immunodeficiency. As of 2023, numerous initiatives using next generation sequencing (NGS) have been announced worldwide including the Genomic Uniform-screening Against Rare Diseases in All Newborns (GUARDIAN study), BeginNGS and Early Check in the USA, BabyScreen+ in Australia, Generation Study by Genomics England, and Screen4Care, Baby Detect in Belgium and PERIGENOMED in France.
Sources: en.wikipedia.org
It is a synthetic compound studied as an agonist of REV-ERB nuclear receptors. It is not an approved medicine and has mainly been examined in laboratory and animal research.
No. It is a small molecule that binds nuclear receptors involved in circadian regulation. Its classification differs from anabolic steroids or peptide hormones.
Published human clinical trial data are lacking. Most safety and activity information comes from preclinical models, so effects in people remain uncertain.
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.