This is a working overview of REV-ERB agonist, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-09-01. Anything still debated is marked as such rather than presented as settled.
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.
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.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ. It is not a steroid, peptide, or natural hormone. In scientific literature, it appears under the code SR9009 and in non-scientific contexts as Stenabolic. The compound was identified through chemical screening efforts aimed at targeting circadian clock components. Its status remains investigational, and no regulatory agency has approved it as a human medicine.
| Property | Value | Notes |
|---|---|---|
| Regulatory status | Not approved for human use | Research-use-only status in many markets |
| WADA status | Prohibited in sport | Generally listed as a non-approved substance |
| Detection technique | LC-MS/MS | Common for urine and blood analysis |
| Common alias | Stenabolic | Informal market nickname, not a pharmacopoeial name |
| Purity check | HPLC or LC-UV | Independent certificate of analysis is typical |
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.
Black Mesa is a 2020 first-person shooter video game developed and published by Crowbar Collective. It is a fan-made remake of Half-Life (1998) in the Source game engine. Originally published as a free mod in September 2012, Black Mesa was approved for commercial release by Valve, the developers of Half-Life. The first commercial version was published as an early-access release in May 2015 with an abridged campaign, followed by a full release in March 2020 restoring the final chapters. Black Mesa was developed in response to Half-Life: Source (2004), Valve's port of Half-Life to the Source engine, which lacked new features or improvements over the original version that used GoldSrc. Two teams wanted to improve on the Source remake and eventually merged to become Crowbar Collective. The project was originally slated to release in 2009, but was pushed back significantly for quality reasons. Adapting Half-Life to an improved version of the Source engine and completely reworking the often-derided final 4 chapters of the game, set outside of the Black Mesa facility on the alien borderworld of Xen, lengthened the development efforts of the remake. Due to its long development time, the modification became notable for its delays on the status of its completion. Major changes include a reskinned collection of textures, models and NPCs, a longer runtime, altered level and puzzle designs, along with different enemy artificial intelligence, and additional dialogue and story elements.
=== Intracellular receptors === Intracellular receptors exist freely in the cytoplasm, nucleus, or can be bound to organelles or membranes. For example, the presence of nuclear and mitochondrial receptors is well documented. The binding of a ligand to the intracellular receptor typically induces a response in the cell. Intracellular receptors often have a level of specificity, this allows the receptors to initiate certain responses when bound to a corresponding ligand. Intracellular receptors typically act on lipid soluble molecules. The receptors bind to a group of DNA binding proteins. Upon binding, the receptor-ligand complex translocates to the nucleus where they can alter patterns of gene expression. Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen (group NR3A) and 3-ketosteroids (group NR3C). In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.
Dean Paul Martin became a tennis player, actor and a captain in the California Air National Guard. He was married to actress Olivia Hussey and figure skater Dorothy Hamill, and was killed while piloting an F-4 Phantom jet in 1987. In 1996, Sundazed Music released The Rebel Kind: The Best of Dino, Desi & Billy, in which all of the group's singles and other non-cover material was collected for the first time on one album. From 1998 to 2010, a reconfiguration of the group, known as "Ricci, Desi, & Billy", performed at various times, in addition to releasing two live albums. The band performed new material and the original hits, with Ricci Martin, the youngest son of singer Dean Martin, replacing his late older brother, Dean Paul Martin. Billy Hinsche died of lung cancer on November 20, 2021, after a short illness. His mother, Celia Hinsche, also died on the same day.
== Career == At the start of his career in 1980, Tanzi worked as a research technologist for James Gusella at Massachusetts General Hospital. There, he assisted in localizing the Huntington's disease gene; their findings were published in Nature in 1983. This was the first study to localize a disease gene purely based on genetic linkage with genomic variants. In 1987, based on his doctoral studies at Harvard Medical School, he was the lead author of seven papers published in Science and Nature between 1987 and 1988, describing the initial cloning, mapping, and characterization of the gene encoding the amyloid beta-protein precursor (APP), the first reported Alzheimer’s disease gene. Two other groups reported the cloning of APP at that time. In 1991-1992, Tanzi and Wilma Wasco, discovered the two APP family members, APLP1 and APLP2. In 1995, Tanzi collaborated with Drs. Peter Hyslop and Jerry Schellenberg to discover the two other EO-FAD genes, presenilin 1 and 2 (PSEN1 and PSEN2). He has published many key studies characterizing the role of the EO-FAD genes in health and disease. All three genes remain among the most highly studied drug targets in the field of AD aimed at reducing beta-amyloid deposition. In 1993, Tanzi first discovered the gene for the neurodegenerative disease, Wilson's disease; his findings were published in Nature Genetics. In that same year, he contributed to the discovery of the first familial amyotrophic lateral sclerosis (ALS) gene, SOD1, by providing the key genetic and physical mapping data for chromosome 21 used to find the gene defect.
Sources: en.wikipedia.org
Corticotropin-like intermediate [lobe] peptide (CLIP), also known as adrenocorticotropic hormone fragment 18-39 (ACTH(18-39)), is a naturally occurring, endogenous neuropeptide with a docosapeptide structure and the amino acid sequence Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe. CLIP is generated as a proteolyic cleavage product of adrenocorticotropic hormone (ACTH), which in turn is a cleavage product of proopiomelanocortin (POMC). Its physiological role has been investigated in various tissues, specifically in the central nervous system. It has been suggested to function as an insulin secretagogue in the pancreas.
=== Familial hypercholesterolemia === The 1985 Nobel Prize for medicine went to two researchers for their work related to familial hypercholesterolemia, which causes large and rapid increases in cholesterol levels. Their research led to the development of statin drugs which are now commonly used to treat high cholesterol.
=== Other applications === Peptide therapeutics such as are attractive for their high specificity and potency, but they often have poor pharmacokinetic profiles due to their degradation by serum proteases. Though O-GlcNAc is generally associated with intracellular proteins, it has been found that engineered peptide therapeutics modified by O-GlcNAc have enhanced serum stability in a mouse model and have similar structure and activity compared to the respective unmodified peptides. This method has been applied to engineer GLP-1 and PTH peptides.
=== Pharmacology === Doxycycline, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. It is used clinically for the treatment of periodontal disease and is the only MMP inhibitor that is widely available clinically. It is sold under the trade name Periostat by the company CollaGenex. Minocycline, another tetracycline antibiotic, has also been shown to inhibit MMP activity. A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies that MMPs are suspected to be involved in (see above). However, most of these, such as marimastat (BB-2516), a broad-spectrum MMP inhibitor, and cipemastat (Ro 32-3555), an MMP-1 selective inhibitor, have performed poorly in clinical trials. The failure of Marimastat was partially responsible for the folding of British Biotech, which developed it. The failure of these drugs has been due largely to toxicity (in particular, musculo-skeletal toxicity in the case of broad spectrum inhibitors) and failure to show expected results (in the case of trocade, promising results in rabbit arthritis models were not replicated in human trials). The reasons behind the largely disappointing clinical results of MMP inhibitors is unclear, especially in light of their activity in animal models.
In most people with Alport syndrome (about 85%), the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure. Alport syndrome can also be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. Past descriptions of an autosomal dominant form are now usually categorized as other conditions. Notably, conditions associated with giant platelets and associated with mutations of MYH9 are no longer considered to be Alport variants. However apparent autosomal dominant transmission of disease associated with mutations in COL4A3 and COL4A4 does occur. Clinical utility gene card for: Alport syndrome.
Sources: en.wikipedia.org
Legality depends on the country and the intended use. In many places it is not approved as a medicine and may be sold only as a research chemical. Importation or possession can be restricted, and sports organizations prohibit it.
Anti-doping laboratories typically use LC-MS/MS to detect SR9009 or its metabolites in urine or blood. The exact assay depends on the laboratory and the testing program. Detection can be challenging because the compound may be rapidly metabolized and present at low levels.
Stenabolic is an informal nickname used in online fitness and research-chemical markets, not an official drug name. It likely references reported effects on endurance in rodent studies. The nickname does not imply approval or proven human benefit.
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.