If you have been reading about freeze-thaw 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 2026-06-17. Numbers and descriptions here follow the published literature rather than marketing material.
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.
Research interest in SR9009 grew from studies showing improved running endurance in mice after short treatment periods. Those experiments linked the compound to increased mitochondrial content and fatty acid oxidation in muscle, but the findings come from animal models and specific dosing schedules. Independent replication has been limited, and the pathways connecting REV-ERB activation to exercise performance are still being mapped. Whether similar responses occur in humans is an open question.
SR9009 is often grouped with compounds studied for circadian and metabolic regulation rather than with classical anabolic steroids. Its interactions with nuclear receptors differ from those of androgen receptor ligands, and its proposed mechanisms involve transcriptional control rather than direct hormone signaling. Some sources classify it as a metabolic modulator because of observed effects on energy utilization. The distinction matters for regulation and for interpreting research results across different compound classes.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic REV-ERB agonist | Small-molecule ligand; not a hormone or peptide |
| Molecular formula | C20H24ClN3O4S | Reported for the free base |
| CAS Registry Number | 1379686-30-2 | Unique chemical identifier |
| Common synonyms | SR9009; stenabolic | Stenabolic is informal and not an official name |
| Reported targets | REV-ERBα and REV-ERBβ | Nuclear receptors linked to circadian and metabolic regulation |
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.
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.
SR9009 stability depends on temperature, moisture, light, and solvent. Solid material is generally kept cool and dry, while solutions may require protection from repeated warming and cooling. Degradation can appear as color changes, precipitate, or new chromatographic peaks. Researchers should follow supplier instructions and their own stability data. Long-term storage conditions for human use have not been established because the compound lacks approved clinical formulation.
SR9009 is supplied as a solid research chemical, often in milligram quantities. Laboratories typically weigh it in a controlled environment because fine powders can disperse. Stock solutions are commonly prepared in dimethyl sulfoxide and stored in small aliquots to reduce freeze-thaw cycles. Personal protective equipment and chemical fume hoods are standard when handling unknown or potent compounds. These practices address laboratory safety rather than human use.
Identity and purity of SR9009 samples are usually checked with chromatographic and spectrometric methods. High-performance liquid chromatography can separate the compound from related impurities, while mass spectrometry provides molecular mass confirmation. Nuclear magnetic resonance spectroscopy may be used for structural verification in research settings. No single method proves biological activity, and certificates of analysis should be reviewed alongside raw data. Independent testing is often needed because online products vary widely.
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.
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.
However, after the East Pakistani Awami League emerged victorious over the Pakistan Peoples Party (PPP), Yahya Khan and the military refused to transfer power. This led to Operation Searchlight, a military crackdown, and eventually sparked the war of liberation by Bengali Mukti Bahini forces in East Pakistan, described in West Pakistan as a civil war rather than a liberation struggle.
The United States Navy announced an operation by the same name in January 2025, using the Navy's Fourth Fleet, focused on integrating "robotic and autonomous systems with traditional naval forces". According to the Miami Herald, Foster Edwards, the 4th Fleet's Hybrid Fleet Director, "described Southern Spear as a significant step in the Navy's evolving Hybrid Fleet Campaign" that would "operationalize a heterogeneous mix of Robotic and Autonomous Systems to support the detection and monitoring of illicit trafficking while learning lessons for other theaters" and "help develop critical techniques and procedures for integrating RAS into the maritime environment." The Operation would use unmanned surface vessels supplied by Saildrone "to monitor illegal activity in the Caribbean and Pacific Ocean", according to Axios. Uncrewed boats for high-risk missions were being used to gather intelligence by June 2025. The United States Southern Command (USSOUTHCOM), whose area of responsibility covers Central and South America and the Caribbean, created a joint task force in October 2025 around the headquarters of II Marine Expeditionary Force (II MEF) tasked with "crushing" the drug cartels operating in the region. Later referred to as the Joint Task Force Southern Spear, its operations are coordinated with the 4th Fleet, the US Navy's component of USSOUTHCOM.
=== Intrinsic resistance === A few Gram-positive bacteria, such as Leuconostoc and Pediococcus, are intrinsically resistant to vancomycin, but they rarely cause disease in humans. Most Lactobacillus species are also intrinsically resistant to vancomycin, except for L. acidophilus and L. delbrueckii, which are sensitive. Other Gram-positive bacteria with intrinsic resistance to vancomycin include Erysipelothrix rhusiopathiae, Weissella confusa, and Clostridium innocuum. Most Gram-negative bacteria are intrinsically resistant to vancomycin because their outer membranes are impermeable to large glycopeptide molecules (with the exception of some non-gonococcal Neisseria species).
=== Role of MMPs in disease === When MMPs are dysregulated, they can make diseases become more aggressive and worsen them instead of curing them. For instance, elevated levels of MMP-1 releases growth factors that enhance cancer metastasis, and in diabetic foot ulcers it slows healing by over-degrading tissues. MMP-8 levels rise in asthma, and in diabetes, it increases the chronic inflammation. MMP-13 drives joint damage in osteoarthritis, while MMP-2 and MMP-9 levels soar in colorectal cancer and heart diseases, carrying out abnormal changes in vessel walls and causing fibrosis. MMP-3 aids rheumatoid arthritis and spine issues, MMP-10 affects bone growth, MMP-7 increases in artery-clogging atherosclerosis, and MMP-12 cause immune cells to overreact, causing severe inflammation. Basically, unchecked MMP activity turns helpful tools into troublemakers.
Sources: en.wikipedia.org
Ardent supporters of Duterte have been labeled as "Diehard Duterte Supporters", alternatively known as "Digong Duterte Supporters", which shares the acronym with the Davao Death Squad (DDS). This label has been applied to the 16 million people who voted for him in the 2016 presidential election. Duterte developed a reputation as a "protector" and "savior" in his hometown of Davao City as mayor of the city for more than two decades. This is despite reports of death squads in the city.
Tourism is a major industry and contributor to the Singaporean economy, attracting 13.6 million international tourists in 2023, more than double Singapore's total population. Tourism contributed directly to about 3% of Singapore's GDP, on average, in the 10 years before 2023, excluding the COVID-19 pandemic years. Altogether, the sector generated approximately 8.6% of Singapore's employment in 2016. Well-known landmarks include the Merlion, the Esplanade, Marina Bay Sands, Gardens by the Bay, Jewel Changi Airport, CHIJMES, National Gallery Singapore, the Singapore Flyer, the Orchard Road shopping belt, the resort island of Sentosa, and the Singapore Botanic Gardens, Singapore's first UNESCO World Heritage Site, all located in southern and eastern Singapore.
== History == At least since the time of Hippocrates, clubbing has been recognized as a sign of disease. The phenomenon has been called "Hippocratic fingers". The Dutch painter Dick Ket had nail clubbing, as is seen from his paintings. He had an underlying disease, probably dextrocardia.
The third is to use an echo-planar readout that dephases magnetization from outside the voxel, also shown to substantially reduce lipid artifacts. All three methods could be combined to overcome lipid contamination. One of the dimensions to understand about a pulse sequence is its coherence pathway. The coherence pathway is the sequence of quantum coherence number(s) the signal takes prior to its acquisition. All coherence pathways end in -1, as this is the only coherence pathway detected by quadrature coils. The spin echo-type sequences (PRESS, sLASER, LASER) simply alternate between +1 and -1. For example, the coherence pathway for PRESS (expressed as a vector) is [-1, 1, -1]. This indicates that after the initial RF pulse (excitation pulse) the spins have a -1 quantum coherence. The refocusing pulses then swap the -1 to +1, then back from +1 to -1 (where it is then detected). Similarly for sLASER the coherence pathway is [-1, 1, -1, 1, -1]. The coherence pathway for LASER is [-1, 1, -1, 1, -1, 1, -1]. The coherence pathway for sPECIAL is [0, 1, -1]. This indicates that after the first RF pulse the signal resides as a population, due to its 0 quantum coherence number. Coherence pathways are critical as the explain how the sequences are affected by crushers and phase cycling. As such, coherence pathway analysis has been used to develop optimized crusher schemes and phase cycling schemes for an arbitrary MRS experiment.
=== Alzheimer's disease === The ATP-binding cassette protein ABCC1 has received attention in the last decade due to its possible connection with Alzheimer's disease. One of the more prominent signs of Alzheimer's disease is the accumulation of β-amyloid proteins in the brain. As these proteins accumulate, they begin to form plaques that interfere with signaling between cells of the nervous system found within the brain. Due to its presence in the choroid plexus and blood-brain barrier and its ability to transport multiple kinds of molecules out of cells, ABCC1 has been a point of interest in many Alzheimer's disease studies. The transporter protein has been shown to decrease β-amyloid accumulation by nearly 80 percent when activated, leading researchers to further investigation on its use in future treatments of Alzheimer's and other neurological disorders.
Sources: en.wikipedia.org
Beginning in the 11th century, European soldiers and knights relied on chain mail for protection of their bodies, and chain armor "shirts" with wide sleeves that hung to the elbow were common. However, it wasn't until the 12th century that chain mail shirts with longer, narrower sleeves began to be worn, and these on occasion had chain mail mittens or "muffs" resembling fingerless gloves and with a pocket for the thumb (though some of these did have complete fingers as well). These attached at the lower edge of the sleeve, and protected the wearer's hands from cuts and lacerations during combat but offered no protection against crushing blows. It wasn't until the early 14th century that armorers began to design fully articulated plate armor: along with this development of the use of plates as a means of protecting the body from blows was the development of hand protection in the form of gauntlets made of overlapping plates of steel. These were created both in the fingerless "mitten" style (which offered plate armor protection and allowed the fingers to share heat but limited the wearer's ability to move those fingers) as well as the fully fingered "glove" style (which though still ungainly and less comfortable in cold weather, permitted full use of all of the fingers). A variety of gauntlet called a "demi-gauntlet" or "demi-gaunt" also came into use around this time. A demi-gaunt is a type of plate armour gauntlet that only protects the back of the hand and the wrist: demi-gaunts are worn with gloves made from chain mail or padded leather.
=== No development reported === AF-130 – purinergic P2X3 receptor antagonist – migraine [40] B-244 (AOB-101; AOB-102; AOB-103; AOB-201; AOB-202; AOB-203; B244; nitrosomonas eutropha D23) – bacteria replacement – migraine [41] Carabersat (SB-204269) – undefined mechanism of action (anticonvulsant) – migraine [42] CLE-500 – undefined mechanism of action – cluster headache [43] CT-044 analogues - CERSCI Therapeutics – reactive oxygen species (ROS) inhibitor – migraine [44] Cyclobenzaprine extended release (Amrix; Bonelax; EUR-1002) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and receptor modulator and other actions) – migraine [45] Donepezil (Allydone; Aricept; E-2020; E-2022; Eranz) – acetylcholinesterase inhibitor – migraine [46] Donitriptan mesilate (F-12640) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [47] Estetrol (E4; Donesta) – estrogen (estrogen receptor agonist) – migraine [48] Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist – migraine [49] Flunarizine (XEN-007) – calcium channel blocker, non-selective monoamine receptor modulator, other actions – migraine [50] Ibudilast (AV-411; Eyevinal; Ibinal; KC-404; Ketas; MN-166; Pinatos) – phosphodiesterase PDE4 inhibitor – headache [51] IPX-232 – undefined mechanism of action – migraine [52] Ketamine hydrochloride intranasal – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – cluster headache [53] Ondansetron/rizatriptan – oral transmucosal film (rizatriptan/ondansetron; MSRX-202) – combination of ondansetron (serotonin 5-HT3 receptor antagonist and antiemetic) and rizatriptan (triptan) [54] Oxytocin (TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist – headache [55] Piroxicam betadex (β-cyclodextrin piroxicam; Brexecam; Brexidol; Brexin; Brexine; Brexinil; CHF 1194; Cicladol; Cycladol; Flogene; piroxicam β-cyclodextrin) – COX inhibitor/NSAID – migraine, tension-type headache [56] Psilocybin (low-dose psilocybin; BPL-PSILO) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache [57] Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache [58] Psilocybin (SYNP-101; synthetic psilocybin) – non-selective serotonin receptor agonist and psychedelic hallucinogen – cluster headache, migraine [59] Relutrigine (PRAX-562) – sodium channel blocker – headache [60] Research programme: calcitonin gene-related peptide receptor antagonists - Merck (CGRP receptor antagonists; Imidazoazepanes; MK-2918; MK-8825) – calcitonin gene-related peptide receptor (CGRPR) antagonists [61] Research programme: GPCR modulators - Nxera Pharma – various actions [62] Research programme: migraine and pain therapeutics - NeurAxon – various actions – migraine [63] Research programme: pain and migraine therapy - OptiNose (OPT-1005) – undefined mechanism of action – migraine [64] Rizatriptan intranasal – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [65] Rizatriptan oral film – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [66] Salubrin (PH80; PH-80; ORG-39479) – vomeropherine – migraine [67] [68] Sumatriptan (Imigran Nasal Spray; Imitrex Nasal Spray) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – menstrual migraine [69] Sumatriptan transmucosal (Omexa) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [70] Zucapsaicin (cis-capsaicin; Civamide; Civanex; Dolorac; Neuroderm; Zuacta) – transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist – cluster headache, migraine [71]
The first Este dukes ruled well and the city achieved an economic and cultural peak: Borso's successor Duke Ercole I had the city of Modena rebuilt according to plans designed by Biagio Rossetti, his successors were patrons of artists like Titian and Ludovico Ariosto. In the War of the League of Cambrai from 1508, troops from Modena fought in Papal service against the Republic of Venice. Upon the death of Duke Alfonso II in 1597, the ducal line became extinct. The Este lands were bequeathed to Alfonso's cousin Cesare d'Este; however, the succession was not acknowledged by Pope Clement VIII and Ferrara was finally seized by the Papacy. Cesare was able to retain Modena and Reggio as Imperial fiefs. In the 1628 War of the Mantuan Succession, the dukes of Modena sided with Habsburg Spain and in turn received the town of Correggio from the hands of Emperor Ferdinand II. During the War of the Spanish Succession, Duke Rinaldo was ousted by French troops under Louis Joseph, Duke of Vendôme, he could not return until 1707. In 1711 the small Duchy of Mirandola was absorbed by the Este. His successor Francesco III backed France in the 1740 War of the Austrian Succession and was expelled by Habsburg forces, but his duchy was restored by the 1748 Treaty of Aix-la-Chapelle. In 1796 Modena was again occupied by a French army under Napoleon, who deposed Duke Ercole III and created the Cispadane Republic out of his territory.
Added in 1974, this stated that parents who did not provide medical treatment for a child for religious reasons would not be considered negligent. States were thereafter obliged to include exemptions or lose funding; the wording of the exemptions made clear that they referred to Christian Science. Largely as a result of lobbying by Children's Healthcare is a Legal Duty (active 1983–2017), the government eliminated the HEW regulation in 1983, but 39 states, as well as Guam and the District of Columbia, still had religious exemptions in their civil codes on child abuse and neglect as of February 2015. As of June 2019, the District of Columbia (Washington, D.C.) and 45 states granted religious exemptions, and 15 granted philosophical exemptions, from laws requiring vaccination. Three states (Arizona, Connecticut, and Washington) say that offering a child treatment from a Christian Science practitioner, "in lieu of medical care", is not regarded as neglect. The state of Washington religious exemption as of September 2019 reads: "It is the intent of the legislature that a person who, in good faith, is furnished Christian Science treatment by a duly accredited Christian Science practitioner in lieu of medical care is not considered deprived of medically necessary health care or abandoned." In 1985 128 people were infected with measles, and three died, at Principia College, a Christian Science school in Elsah, Illinois. In 1994, 190 people in six states were infected with measles traced to a child from a Christian Science family in Elsah.
=== Agentic misalignment === "Agentic misalignment" refers to situations in which an AI agent's actions or goals diverge from its designers' intentions. This occurs when an autonomous system pursues unintended strategies to achieve its objectives, a concern studied in AI safety research. Potential examples include AI agents attempting to sabotage an organization's systems when facing updates or deactivation. On July 21, 2026, OpenAI disclosed that during a capture the flag cybersecurity test, an unreleased AI model autonomously evaded containment restrictions, gained access to the public internet, and compromised Hugging Face, a platform where developers host and share AI models and datasets. Contributing factors to the incident were a lack of log monitoring of the software activities and inadequate sandboxing. On September 24, 2026, it was announced that an internal OpenAI frontier model autonomously gained unauthorized access on June 18 to the Medicare Statistics Reporting Service, an Australian Government website that holds data on the country's universal health insurance scheme Medicare. This was described as the first known case of an AI agent hacking a government network and has furthered concern about AI safety and loss-of-control. In response to these hacks, OpenAI announced that it would slow model development, including a two-week pause on reinforcement learning of its latest models to "assess model behavior, validate our safeguards, and establish more evidence of alignment before proceeding".
Sources: en.wikipedia.org
SR9009 is a synthetic compound investigated as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is used in preclinical research on circadian rhythm and metabolism. It is not an approved drug.
No. It has no approved medical indication, and human safety and efficacy data are limited. It appears in research chemical markets and is banned by some sports authorities.
Natural ligands include heme and certain metabolites; SR9009 is a synthetic small molecule with higher potency and selectivity in some assays. Its effects depend on cell type and timing. It is not a naturally occurring compound.
It is a synthetic REV-ERB agonist used mainly in preclinical research. It is not an approved medicine for human use.