nuclear receptor 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 2026-08-01 and is reviewed periodically as new material appears.
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.
REV-ERB proteins typically suppress gene expression by recruiting corepressor complexes to DNA response elements. SR9009 binds these receptors and strengthens that repressive action in cell-based assays. Studies in rodents have reported changes in lipid handling, mitochondrial function, and exercise capacity after treatment. Such findings are often cited as evidence for metabolic effects, but species differences and limited pharmacokinetic data make direct translation to humans uncertain. Researchers continue to examine which effects are robust and which depend on specific experimental conditions.
SR9009 is frequently discussed alongside other REV-ERB ligands, including synthetic agonists and natural heme-related molecules. Its selectivity for REV-ERB over related nuclear receptors has been measured in binding and reporter assays, though off-target activity at higher concentrations is possible. The compound is prohibited in sport by the World Anti-Doping Agency, and it is not approved for any medical use in major jurisdictions. Products sold online may be labeled as research chemicals, and their identity and purity are not guaranteed by regulatory review.
SR9009 is a synthetic small molecule that acts on the nuclear receptors REV-ERBα and REV-ERBβ. These receptors are part of the circadian clock machinery and normally repress transcription of certain target genes. In laboratory research, SR9009 is used as a chemical tool to study how REV-ERB activity influences metabolism, inflammation, and daily biological rhythms. The compound is not an approved medicine, and its effects in humans remain largely uncharacterized. It is often described as an investigational agent rather than a therapeutic product.
| 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 |
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.
Regulatory agencies have not approved SR9009 for human therapeutic use. It is typically sold as a research chemical with labels stating that it is not for human consumption. The World Anti-Doping Agency prohibits the substance in sport, generally under the category of non-approved substances. Customs and national laws may restrict importation, sale, or possession. Product quality and legal status can vary by country and vendor, and therapeutic claims are not permitted in regulated advertising because the compound lacks approval.
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.
SR9009 is a synthetic small molecule studied as an agonist of REV-ERB nuclear receptors. REV-ERB alpha and REV-ERB beta help regulate circadian rhythms and metabolic gene expression. In laboratory research, SR9009 has been used to probe how these receptors affect skeletal muscle, liver, and adipose tissue. The compound was identified in academic drug-discovery work and is often described in scientific literature by its chemical name and research code. It is not an approved medicine, and human clinical data remain limited or absent.
SR9009 is frequently discussed in fitness and research-chemical contexts, yet it has no approved medical indication. Regulatory agencies have not authorized it for human use, and it is not a standard prescription drug. Some sports organizations list it as a prohibited substance because of its potential performance-enhancing properties. Published human data are sparse, so claims about its effects in people often rely on animal models or anecdotal reports. Quality and identity of online materials can vary widely.
SR9009 is a synthetic small molecule studied as a REV-ERB agonist. REV-ERBα and REV-ERBβ are nuclear receptors that help regulate circadian rhythms and metabolic gene expression. The compound was identified in academic screening efforts to find synthetic ligands for these receptors. In cell and animal studies, SR9009 alters transcription of genes involved in lipid and glucose metabolism, and it can shift circadian behavior. It is not an approved therapeutic agent.
Mechanistically, SR9009 binds the ligand-binding domain of REV-ERBα/β and enhances recruitment of corepressor complexes. This represses target genes rather than activating them. Because REV-ERB proteins normally compete with ROR proteins at shared response elements, the net effect depends on tissue and timing. Researchers use SR9009 to probe how nuclear receptor signaling links the clock to metabolism, inflammation, and muscle biology. Findings are largely preclinical, and the precise contribution of each receptor subtype remains under study.
Stability depends on physical form, temperature, light exposure, and solvent. Solid SR9009 is generally stored cold and dry, with protection from light to limit degradation. Dimethyl sulfoxide stocks are common for laboratory work, but repeated freeze-thaw cycles can reduce compound integrity. Aqueous solutions may be less stable than organic stocks, and the ethyl ester in the structure can be susceptible to hydrolysis under certain conditions. Researchers typically validate storage conditions and recheck purity before quantitative experiments, especially when using archived material.
Regulatory treatment of SR9009 varies by country and region. It is not approved as a pharmaceutical, and several jurisdictions restrict its sale for human consumption. Some authorities classify it as a research chemical, a prescription-only substance, or a prohibited performance-enhancing agent in sport. Purchasers may encounter certificates of analysis, but these documents do not guarantee identity, purity, or legality. In research settings, institutional safety reviews and controlled procurement help ensure that materials are handled under appropriate oversight. The absence of harmonized rules means that legal status can change and requires verification.
Analytical identification of SR9009 typically relies on liquid chromatography coupled with tandem mass spectrometry. In biological samples, researchers first separate the compound from matrix components using protein precipitation, liquid-liquid extraction, or solid-phase extraction. High-performance liquid chromatography with ultraviolet detection and nuclear magnetic resonance spectroscopy can support structural confirmation of reference materials. Because SR9009 is a small, relatively lipophilic molecule, reverse-phase columns and acidic mobile phases are common. Laboratories often include isotope-labeled internal standards to improve quantification and to correct for ion suppression.
The United States was the biggest foreign investment source and one of Malaysia's closest allies during Mahathir's rule. A 2003 house hearing by the Subcommittee on East Asia and the Pacific of the U.S. House International Relations Committee (now called the House Committee on Foreign Affairs) summarises the relationship between the United States and Malaysia as follows: "Despite sometimes blunt and intemperate public remarks by Prime Minister Mahathir, U.S.-Malaysian cooperation has a solid record in areas as diverse as education, trade, military relations, and counter-terrorism." Mahathir was publicly critical of the foreign policy of the United States, particularly during George W. Bush's presidency. He has also condemned the US-led war on Iraq and Afghanistan. In 1984, during his first visit to the United States, Mahathir received a warm welcome. He met President Ronald Reagan in the Oval Office, followed by discussions, lunch, and a press conference. He also made a private visit to Tulsa, Oklahoma. Reagan said he and Mahathir "had a valuable exchange of views on international and bilateral issues and found ourselves in agreement to a remarkable degree", but acknowledged differences in Middle East policy. In the years that followed, Mahathir held informal meetings with US presidents George H. W. Bush, Bill Clinton, and George W. Bush at various locations to discuss issues related to palm oil and the United States' attitude towards Muslim countries. In January 1997, Mahathir visited the United States to promote Malaysia's Multimedia Super Corridor.
=== Floriculture === Many species of Lilieae (in genera Tulipa, Fritillaria, Lilium, and Erythronium) and Calochortoideae (Calochortus and Tricyrtis) are grown as ornamental plants worldwide. Within these genera a wide range of cultivars have been developed by breeding and hybridisation. They are generally used in outdoor gardens and other displays, although in common with many bulbous flowering plants they are often induced to bloom indoors, particularly during the winter months. They also form a significant part of the cut flower market, in particular Tulipa and Lilium.
=== Effect of Stimuli on the Release of TSH === Multiple neurogenic stimuli are known to affect the release of TSH from thyrotropes. Exposure to cold temperatures increases the secretion of TSH. This increased secretion results from the increased secretion of TRH, as the hypothalamus is excited by the change in body temperature. Furthermore, emotions that activate the sympathetic nervous system—such as excitement and anxiety—decrease the secretion of TSH. The decrease in secretion is also connected to the change in body temperature. Activation of the sympathetic nervous system increases the body temperature, which then causes a decrease in TRH secretion and the subsequent decrease in TSH secretion. Thyroid hormones can have a direct inhibitory effect on thyrotropic cells, though the exact mechanism is unknown. At elevated levels of thyroxine, the rate of secretion of TSH decreases to near zero, as the body tries to maintain a relatively constant level of thyroid hormone in circulation. However, the inhibitory effect of thyroid hormones may decrease in thyrotropic tumor cells. The receptor affinity for T3 significantly decreases for thyrotropic tumor cells in culture when compared to healthy thyrotropes, which reduces the regulatory effect. In addition, during pregnancy, the size of the pituitary gland increases, and consequently, the expression of TSH also increases. This increase in secretion of TSH likely results from the additional metabolic load that pregnant mothers experience in combination with the secretion of placental hormones.
== Activities in the United States == The Ethiopian Pacific Movement and the Peace Movement of Ethiopia (both African-American black nationalist organizations) claimed they were affiliated with the Black Dragon Society. Mittie Maude Lena Gordon, who led the Peace Movement of Ethiopia, claimed to be personally affiliated with the Kokuryūkai. On March 27, 1942, FBI agents arrested members of the Black Dragon Society in the San Joaquin Valley, California. In the Manzanar Internment Camp, a small group of pro-Imperial Japanese flew Black Dragon flags and intimidated other Japanese inmates.
Sources: en.wikipedia.org
=== Drug design of RXPA 380 === RXPA380 was the first inhibitor that was highly selective of the C-domain of ACE, it has the formula Phe-Phe-Pro-Trp. The development of this compound was built on researches that showed that some bradykinin-potentiating peptides showed selectivity for the C-domain and all had several prolines in their structure. These observations lead the researchers to synthesize phosphinic peptides containing a proline residue in the P1’ position and evaluating these compounds led to the discovery of RXPA380. To study the roles of the residues on RXPA380 the researchers made 7 analogues of RXPA380. All of the compounds made were obtained as a mixture of either 2 or 4 diastereoisomers but all of them were easily resolved and only one of them was potent. This is consistent with the initial modeling studies of RXPA380 which showed that only one diastereomer could accommodate in the active site of germinal ACE. Analogues where pseudo-proline or tryptophan residues had been substituted showed less selectivity than RXPA380. This is probably because these two analogues have more potency toward the N-domain than RXPA380 does. Substituting both of these residues gives great potency but none selectivity. This shows that pseudo-proline and tryptophan residues accommodate well in the C-domain but not in the N-domain. Two more analogues with both pseudo-proline and tryptophan but missing the pseudo-phenylalanine residue in P1 position showed low potency for N-domain, similar to RXPA380.
Starting material is plasma that has been pretreated by centrifugation, A round of gel filtration is run, ion exchange on DEAE Sepharose is run to bind the albumin to the column, Albumin is eluted with a sodium acetate buffer, and Final polishing with gel filtration. The end result is a highly pure and safe batch of albumin that is 100% non-pyrogenic, sterile, and free of active HIV virus. The product purity is greater than 98% and the protein content is about 50 g/L.
== Non-state actors == Hamas: Hamas strongly condemned the strikes on Venezuela, calling them a "grave violation of international law" and an "assault on the sovereignty of an independent state," adding that it "represents a continuation of America's unjust policies and interferences, which are driven by its imperial ambitions." Hezbollah: Hezbollah condemned what it called "the terrorist aggression and American thuggery against the Bolivarian Republic of Venezuela," and added that it "further affirms its full solidarity with Venezuela — its people, presidency, and government — in confronting this American aggression and arrogance." It added that "The US is gripped by a craze for control, especially under the current president, and continues its aggressive polices based on subjugating free nations and peoples, plundering their wealth and resources, and leading wars aimed at redrawing borders." Popular Front for the Liberation of Palestine: The Popular Front for the Liberation of Palestine condemned the attack, asserting it to be akin to Israeli aggression against Palestinians. The group affirmed that they stood with Venezuela on all fronts and that vowed that the nation ("Venezuela - 'Bolivar, Chávez, and Maduro'") would emerge victorious. SPC: The Houthi-led government in Yemen condemned the United States as "terrorists," stating "What America is doing to Venezuela proves once again that America is the head of evil and the mother of terrorism. Yemen affirms solidarity with Venezuela and its President Nicolás Maduro, who has refused to submit to American hegemony."
Overall the missing information include[s] quantitative data on the composition and specifications of yohimbe bark and its preparations used in food and food supplements covering other alkaloids besides yohimbine, data on the bioavailability of active ingredients from the yohimbe bark extract and data on the toxicity of well specified individual preparations of yohimbe bark and the major yohimbe bark alkaloids, especially regarding subchronic toxicity, genotoxicity and reproductive toxicity. One study found that samples of brands sold in American brick-and-mortar stores contained highly variable amounts of yohimbine, with some brands of "yohimbe" not containing yohimbine from the P. johimbe tree, and other products containing no yohimbine at all. Labeling claims were often misleading. In analyses by other laboratories for products sold in the US, in other countries, and on the internet, highly variable content levels of yohimbine were revealed. Yohimbe sold in markets in West Africa where the tree grows may be adulterated with other species of the genus Pausinystalia, which contain little yohimbine. The amounts of alkaloid found even in genuine P. johimbe bark vary considerably, depending on the source of the bark (roots, stem, branches, height).
=== Cost === Irradiation is a capital-intensive technology requiring a substantial initial investment, ranging from $1 million to $5 million. In the case of large research or contract irradiation facilities, major capital costs include a radiation source, hardware (irradiator, totes and conveyors, control systems, and other auxiliary equipment), land (1 to 1.5 acres), radiation shield, and warehouse. Operating costs include salaries (for fixed and variable labor), utilities, maintenance, taxes/insurance, cobalt-60 replenishment, general utilities, and miscellaneous operating costs. Perishable food items, like fruits, vegetables and meats would still require to be handled in the cold chain, so all other supply chain costs remain the same. Food manufacturers have not embraced food irradiation because the market does not support the increased price of irradiated foods, and because of potential consumer backlash due to irradiated foods. The cost of food irradiation is influenced by dose requirements, the food's tolerance of radiation, handling conditions, i.e., packaging and stacking requirements, construction costs, financing arrangements, and other variables particular to the situation.
Sources: en.wikipedia.org
These adverse effects were reversed when the regimen stopped, but it was fatal in some patients with protracted vomiting. Milk-alkali syndrome declined in men after effective treatments for peptic ulcer disease arose. Since the 1990s it has been most frequently reported in women taking calcium supplements above the recommended range of 1.2 to 1.5 grams daily, for prevention and treatment of osteoporosis, and is exacerbated by dehydration. Calcium has been added to over-the-counter products, which contributes to inadvertent excessive intake. Excessive calcium intake can lead to hypercalcemia, complications of which include vomiting, abdominal pain and altered mental status. As a food additive it is designated E170, and it has an INS number of 170. Used as an acidity regulator, anticaking agent, stabilizer or color it is approved for usage in the EU, US and Australia and New Zealand. It is "added by law to all UK milled bread flour except wholemeal". It is used in some soy milk and almond milk products as a source of dietary calcium; at least one study suggests that calcium carbonate might be as bioavailable as the calcium in cow's milk. Calcium carbonate is also used as a firming agent in many canned and bottled vegetable products. Several calcium supplement formulations have been documented to contain the chemical element lead, posing a public health concern. Lead is commonly found in natural sources of calcium.
CNS excitation: nervousness, agitation, anxiety, apprehension, tingling around the mouth (circumoral paraesthesia), headache, hyperesthesia, tremor, dizziness, pupillary changes, psychosis, euphoria, hallucinations, and seizures CNS depression with heavier exposure: drowsiness, lethargy, slurred speech, hypoesthesia, confusion, disorientation, loss of consciousness, respiratory depression, and apnoea. Cardiovascular: hypotension, bradycardia, arrhythmias, flushing, venous insufficiency, increased defibrillator threshold, edema, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression. Respiratory: bronchospasm, dyspnea, respiratory depression or arrest Gastrointestinal: metallic taste, nausea, vomiting, agita, and diarrhea Ears: tinnitus Eyes: local burning, conjunctival hyperemia, corneal epithelial changes/ulceration, diplopia, visual changes (opacification) Skin: itching, depigmentation, rash, urticaria, edema, angioedema, bruising, inflammation of the vein at the injection site, irritation of the skin when applied topically Blood: methemoglobinemia Allergy ADRs associated with the use of intravenous lidocaine are similar to the toxic effects of systemic exposure above. These are dose-related and more frequent at high infusion rates (≥3 mg/min). Common ADRs include headache, dizziness, drowsiness, confusion, visual disturbances, tinnitus, tremor, and/or paraesthesia.
In an interview on a day with record hospitalizations, Melo asked that the people of the city contribute with their lives to save the economy of the city: "Contribute with your family, your city, your life, so that we can save the economy of the municipality of Porto Alegre." The statement generated controversy nationally and internationally. Just a day after reaching record levels, the leader of Melo's government in the Municipal Chamber of Porto Alegre, Idenir Cecchim, accused the director of the Hospital de Clínicas of "spreading terror" in giving alerts about the overcrowding at the institution. Ahead of the imminent collapse of the city's health system, governor Eduardo Leite decided to decree the entirety of the state of Rio Grande do Sul under the black flag category starting on 27 February, with no possibility of co-management. Melo asserted that he disagreed with Leite's decision, but would still comply. The mayor, however, continued to criticize, through social media, the more restrictive rules to slow down the spread of COVID-19 that were implemented by the state government. On 28 February, hospital beds reached 100% capacity for the first time and still continued to rise, with the wait list for beds also increasing. The overcrowding indicated that part of the services for patients in beds would be improvised.
== Genetic methods == The yeast two-hybrid and bacterial two-hybrid assays investigate interactions between artificial fusion proteins. They do not require isolation of proteins but rather use transformation to express proteins in yeast or bacteria, respectively. The cells are designed in a way that an interaction activates the transcription of a reporter gene or a reporter enzyme. These methods allow easy screening of interactions and libraries with high throughput (see two-hybrid screening).
== Function and regulation == Most of the glucokinase in a mammal is found in the liver, and glucokinase provides approximately 95% of the hexokinase activity in hepatocytes. Phosphorylation of glucose to glucose-6-phosphate (G6P) by glucokinase is the first step of both glycogen synthesis and glycolysis in the liver. When ample glucose is available, glycogen synthesis proceeds at the periphery of the hepatocytes until the cells are replete with glycogen. Excess glucose is then increasingly converted into triglycerides for export and storage in adipose tissue. Glucokinase activity in the cytoplasm rises and falls with available glucose. G6P, the product of glucokinase, is the principal substrate of glycogen synthesis, and glucokinase has a close functional and regulatory association with glycogen synthesis. When maximally active, GK and glycogen synthase appears to be located in the same peripheral areas of hepatocyte cytoplasm in which glycogen synthesis occurs. The supply of G6P affects the rate of glycogen synthesis not only as the primary substrate, but by direct stimulation of glycogen synthase and inhibition of glycogen phosphorylase. Glucokinase activity can be rapidly amplified or damped in response to changes in the glucose supply, typically resulting from eating and fasting. Regulation occurs at several levels and speeds, and is influenced by many factors that affect mainly two general mechanisms:
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 research compound that binds and modulates the nuclear receptors REV-ERBα and REV-ERBβ. It is used in laboratory studies of circadian biology and metabolism, not as an approved medicine. It is also known by the informal name Stenabolic.