NR1D2 is one of those subjects where the details matter more than the headlines. This page pulls together the background, the mechanisms, and the practical points readers ask about most.
Updated 2026-04-28. Numbers and descriptions here follow the published literature rather than marketing material.
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 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.
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.
| 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. |
In rodent studies, SR9009 has been reported to increase mitochondrial content in skeletal muscle and improve exercise endurance under some conditions. These findings led to popular descriptions such as an exercise mimetic, although that term oversimplifies the biology. Effects vary by dose, timing, tissue, and model. The compound's influence on circadian pathways means that time of administration can matter in experiments. Whether similar metabolic changes occur in humans remains largely unexplored in controlled published trials.
Pharmacokinetic data for SR9009 are limited in published literature. Some reports indicate low oral bioavailability and rapid clearance in animals, which complicates interpretation of exposure and effect. Researchers often use injected routes in preclinical work to achieve measurable systemic levels. Analytical studies rely on mass spectrometry to detect the parent compound and its metabolites. Questions about tissue distribution, active metabolites, and long-term consequences remain open. Species differences in metabolism can affect observed half-life and target engagement.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is not an approved medicine and has no established human therapeutic use. The compound appears in scientific literature as a tool for probing circadian and metabolic regulation. Online sellers often label it as a research chemical, sometimes using the nickname Stenabolic. Its chemical identity is distinct from selective androgen receptor modulators, stimulants, and peroxisome proliferator-activated receptor delta agonists. Researchers use it mainly in cell and animal experiments.
At the molecular level, SR9009 binds REV-ERBα and REV-ERBβ and alters their repressive activity on target genes. These nuclear receptors help regulate the circadian clock, lipid synthesis, glucose metabolism, and inflammatory pathways. By changing transcription, the compound can shift the timing or magnitude of downstream metabolic processes in model systems. It does not act through androgen receptors or adenosine receptors, which distinguishes it from several substances sold for athletic performance. Whether the same transcriptional changes occur in humans at tolerable exposures remains an open question because controlled human studies are lacking.
Preclinical reports describe effects on exercise endurance, mitochondrial content, and lipid profiles in rodents, but these findings come from specific experimental conditions. Many studies use high doses or delivery methods that may not translate directly to human use. SR9009 has been reported to have low oral bioavailability and a short half-life, which complicates interpretation of oral dosing studies. It is not established as safe or effective for any indication. Literature discussions often separate its pharmacological mechanism from unverified claims made in fitness and supplement markets.
== Structure and functions == Cryo-electron microscopy (Cryo-EM) study has revealed the structural architecture of PLOD3 within the lysyl O-linked glycosylation complex (KOGG complex), which plays a crucial role in procollagen maturation. The KOGG complex consists of a PLOD3 (LH3) dimer, a Procollagen galactosyltransferase 1 (ColGalT1) dimer, and UDP-bound cofactors, orchestrating the hydroxylation (by PLOD3) and dual glycosylation (galactosylation by ColGalT1 and glucosylation by PLOD3) of lysine residues in the endoplasmic reticulum (ER) lumen. These modifications are essential for collagen cross-linking, fibrillogenesis, and overall structural integrity. Additionally, the structural study suggests that the KOGG complex can polymerize into a larger, fiber-like enzyme supercomplex, which may further regulate collagen modification and assembly. Defects in PLOD3 function or glycosylation efficiency have been implicated in connective tissue disorders, including osteogenesis imperfecta and fibrosis-related diseases.
==== Established in the first team ==== Now back at Tottenham, Townsend started the second Premier League match of their 2013–14 season, and went on to make a total of 33 appearances, including 25 in the league. He scored twice, in a 5–0 away victory over Dinamo Tbilisi in the Europa League (his first match of the season), and his first in the Premier League in a 2–0 victory away to Aston Villa on 20 October 2013. In the middle of the season, Townsend came under the management of his third Tottenham boss, after Villas-Boas was replaced by Tim Sherwood. Sherwood's contract was terminated at the end of the season, and Townsend started the 2014–15 season under new manager Mauricio Pochettino. He made a total of 35 appearances, scoring five goals, but was reduced to just 17 appearances in the league, having been unable to hold down a starting place until the second half of the season. He started as Tottenham lost 2–0 to Chelsea in the 2015 League Cup Final at Wembley Stadium on 1 March. Having had nine loan spells, Townsend's career path to regular first team football for Tottenham is often discussed in the context of a wider debate in English football about the best way to develop young talent, contrasting the loan route with Premier League players being developed in Under-21 leagues, or being brought to the Premier League level via transfers from lower league clubs.
=== Occurrence === All berkelium isotopes have a half-life far too short to be primordial. Therefore, any primordial berkelium − that is, berkelium present on the Earth during its formation − has decayed by now. On Earth, berkelium is mostly concentrated in certain areas, which were used for the atmospheric nuclear weapons tests between 1945 and 1980, as well as at the sites of nuclear incidents, such as the Chernobyl disaster, Three Mile Island accident and 1968 Thule Air Base B-52 crash. Analysis of the debris at the testing site of the first United States' first thermonuclear weapon, Ivy Mike, (1 November 1952, Enewetak Atoll), revealed high concentrations of various actinides, including berkelium. For reasons of military secrecy, this result was not published until 1956. Nuclear reactors produce mostly, among the berkelium isotopes, berkelium-249. During the storage and before the fuel disposal, most of it beta decays to californium-249. The latter has a half-life of 351 years, which is relatively long compared to the half-lives of other isotopes produced in the reactor, and is therefore undesirable in the disposal products. The transuranic elements up to fermium, including berkelium, should have been present in the natural nuclear fission reactor at Oklo, but any quantities produced then would have long since decayed away.
Sources: en.wikipedia.org
== Company history == Digico was founded in 1965 by Keith Trickett and Avo Hiiemae, two ex-ICL electronics engineers. Former MP Eric Lubbock was chairman from 1969 to 1983. The company was based in Letchworth initially, moving to a new factory in Stevenage in 1973 and employing about 90 staff. Digico's first product was a laboratory data-logging and spectrum analyser hardware system named DIGIAC. A prototype had been developed before Digico was formed, by the founders in a garage, so became an immediate source of income. Digico soon developed a 16-bit minicomputer series, the Micro 16, for which it was best known for. In 1974 Digico had a turnover of over £1 million (equivalent to £9 million in 2025) and in 1977 well over £1 million. Spanverne Investments raised a large private capital investment into Digico in 1981, while the new Prince product was being developed. In October 1982, Digico announced it would close its Stevenage factory with the loss of 130 jobs within six months. This was part of a rationalisation plan to concentrate manufacturing at its large Leeds site. It would retain its Letchworth site primarily as a south England office. On 1 February 1984, the Financial Times reported that after a weekend of failed negotiation between British computer company Optim and Midland Bank, Digico went into receivership on 30 January 1984. Digico owed more that £400,000 to Midland Bank and over £1 million to other creditors.
The club was founded by members of the Royal Agricultural Society, the Melbourne Hunt Club and the Victorian Woolbrokers. The Essendon Football Club is thought to have been formed in 1872 at a meeting in the home of a well-known brewery family, the McCrackens, whose Ascot Vale property hosted a team of local junior players. Robert McCracken (1813–1885), the owner of several city hotels, was the founder and first president of the Essendon Football Club, and his son, Alex McCracken, its first secretary. Alex later became president of the newly formed VFL. Alex's cousin Collier McCracken, who had already played with Melbourne, was the team's first captain. The club played its first recorded match against the Carlton Second Twenty (the reserves) on 7 June 1873, with Essendon winning by one goal. Essendon played 13 matches in its first season, winning seven, with four draws and losing two. The club was one of the inaugural junior members of the Victorian Football Association (VFA) in 1877, and it began competing as a senior club from the 1878 season. During its early years in the Association, Essendon played its home matches at Flemington Hill, but it moved to the East Melbourne Cricket Ground in 1881. In 1878, at Flemington Hill, Essendon played its first match on what would be considered by modern standards to be a full-sized field. In 1879, Essendon played Melbourne in one of the earliest night matches recorded when the ball was painted white.
It predominantly affects children between the ages of two and six years in the least developed countries around the world, primarily in sub-Saharan Africa. Noma survivors experience stigma, social isolation, and discrimination within their communities. These can be countered by education and community outreach programs.
The glaucophyte chloroplast group is the smallest of the three primary chloroplast lineages as there are only 25 described glaucophyte species. Glaucophytes diverged first before the red and green chloroplast lineages diverged. Because of this, they are sometimes considered intermediates between cyanobacteria and the red and green chloroplasts. This early divergence is supported by both phylogenetic studies and physical features present in glaucophyte chloroplasts and cyanobacteria, but not the red and green chloroplasts. First, glaucophyte chloroplasts have a peptidoglycan wall, a type of cell wall otherwise only in bacteria (including cyanobacteria). Second, glaucophyte chloroplasts contain concentric unstacked thylakoids which surround a carboxysome – an icosahedral structure that contains the enzyme RuBisCO responsible for carbon fixation. Third, starch created by the chloroplast is collected outside the chloroplast. Additionally, like cyanobacteria, both glaucophyte and rhodophyte thylakoids are studded with light collecting structures called phycobilisomes.
Sources: en.wikipedia.org
1. Leading theorists wedded to the standard interpretations that allow them to dominate their field, tend first to deny that the anomaly exists; at most, it is a 'blip', an unimportant or transient factor. Initially, structural Realists sought to deny that unipolarity was enduring or important, and predicted its quick demise. Waltz, Mearsheimer, and Layne all predicted in the early 1990s that other powers would soon emerge to balance the US.2. As the salience of the anomaly becomes undeniable, theoreticians redefine or shift their theoretical expectations, so as to contend that the anomaly can indeed be explained by their original theory even if their earlier writings ruled it out. More recently, many structural Realists have acknowledged the existence of unipolarity, or at least have acknowledged the absence of traditional balancing against the US, but have altered standard definitions of balancing behavior in order to reconcile this with balance-of-power theory. Thus, Mearsheimer suggested that Iran and North Korea are balancing, even though the "balance" is not in sight.3. Finally, a band of younger scholars, less invested professionally in the old theory, develops a new interpretation that not only explains the anomaly but places it at its theoretical center. This new theoretical interpretation supersedes the old one and becomes the new 'paradigm' for successive inquiry. In this manner, Robert Pape, T. V.
=== Discontinued === Balovaptan (RG-7314, RO-5028442, RO-5285119) – vasopressin V1A receptor antagonist Blarcamesine (AE-37, ANA001, ANAVEX 2-73) – sigma σ1, muscarinic acetylcholine M1, and ionotropic glutamate NMDA receptor agonist Brilaroxazine (RP-5063, RP-5000) – dopamine D2, D3, D4 receptor partial agonist, serotonin 5-HT1A receptor agonist, serotonin 5-HT2A, 5-HT2B, 5-HT7 receptor antagonist, and atypical antipsychotic Bumetanide oral liquid (S-95008) – sodium–potassium–chloride symporter/cotransporter inhibitor and indirect GABAergic inhibitor discontinued after failed phase 3 trial Carbetocin (CYP-2001) – oxytocin receptor agonist CX-516 (1-BCP; BDP-12, SPD-420; AMPAlex) – AMPA receptor modulator EM-036 (memantine analogue) – ionotropic glutamate NMDA receptor antagonist, other actions Fasoracetam (AEVI-001, LAM-105, MDGN-001, NFC-1, NS-105) – various actions and racetam Fluoxetine rapid-dissolve (AT-001; AT001; NPL-2008; Serelsa; Zydis™ ODT fluoxetine) – serotonin reuptake inhibitor GTS-21 (DMXB-A, DMXB-A sustained release, DMXB-A-SR) – α7 nicotinic acetylcholine receptor partial agonist Ketamine intranasal (RVT-701) – ionotropic glutamate NMDA receptor antagonist Memantine (Namenda) – ionotropic glutamate NMDA receptor antagonist, other actions Oxytocin intranasal (Syntocinon Nasal Spray; TUR 001) – oxytocin receptor agonist Research programme: AMPA receptor agonists (ampakines, AMPAkines; CX compounds) - RespireRx – ionotropic glutamate AMPA receptor agonists Research programme: NMDA receptor modulators - AbbVie/Naurex (NRX-1050; NRX-1051; NRX-1059; NRX-105x; NRX-1060; NRX-2085; NRX-20xx) – ionotropic glutamate NMDA receptor modulators Risperidone extended-release (Risperisphere) – dopamine D2 and D3 receptor antagonist, serotonin 5-HT1B, 5-HT2A, 5-HT2C, and 5-HT7 receptor antagonist or inverse agonist, α1- and α2-adrenergic receptor antagonist, histamine H1 receptor inverse agonist, and atypical antipsychotic Secretin (INN-329, RG-1068; SecreFlo) – medical imaging enhancer (diagnosis) Suramin (Antrypol) – DNA-directed DNA polymerase inhibitor and intercellular signaling peptide/protein inhibitor Trichuris suis ova (CNDO-201, TSO, TSO-2500, TSO-7500) – immunomodulator Trofinetide (Daybue; G-2Me-PE; Glycyl-2-methyl-L-prolyl-L-glutamic acid; NNZ-2566; IGF-1 (1–3) analogue) – unknown / various actions
Prolactin-releasing peptide (PrRP) is a peptide hormone that in humans is encoded by the PRLH gene. PrRP binds to the receptor PrRPR and seems to be involved in appetite regulation, but its precise function isn’t fully understood. Though early research suggested that PrRP stimulates prolactin (PRL) release, hence its name, this potential function is debated. Unlike other anterior pituitary hormones, the hypothalamus seems to primarily regulate prolactin release through inhibition, mostly via dopamine as part of the hypothalamic–pituitary–prolactin axis.
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.
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.