A practical reference on REV-ERB agonist: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2025-10-10. Anything still debated is marked as such rather than presented as settled.
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.
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.
Physicochemical behavior influences handling. SR9009 is described as a solid with limited aqueous solubility, so organic solvents such as dimethyl sulfoxide or ethanol are common in research stock solutions. Aqueous dilution can produce precipitates if the organic content is too low. Light, heat, and repeated freeze-thaw cycles may affect stability. Storage recommendations usually specify a desiccated freezer environment protected from light, but exact stability data depend on the formulation and matrix.
Detection in biological samples can be complicated by rapid metabolism and low circulating concentrations. Some studies report phase I and phase II metabolites, and analytical methods may need to target those species in addition to the parent compound. Immunoassays are not broadly available, so mass spectrometry remains the main confirmatory approach. For anti-doping testing, laboratories look for SR9009 and its metabolites using validated LC-MS methods. Open questions include how long metabolites remain detectable and how different routes of administration alter detection windows.
| Property | Value | Notes |
|---|---|---|
| Common name | SR9009 | Also marketed informally as Stenabolic |
| Chemical class | Synthetic REV-ERB agonist | Binds REV-ERBα and REV-ERBβ |
| Molecular formula | C24H30ClN3O4S | Approximate molecular weight 492 g/mol |
| CAS Registry Number | 1379686-30-2 | Identifier for the parent compound |
| Regulatory status | Not approved for human use | Prohibited in sport by WADA |
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.
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.
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity.); capsaicin also is used topically. Lidocaine, an anesthetic, and steroids may be injected into joints for longer-term pain relief. Lidocaine is also used for painful mouth sores and to numb areas for dental work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the bloodstream when applied in large doses to the skin without medical supervision. These topical anesthetics contain anesthetic drugs such as lidocaine, tetracaine, benzocaine, and prilocaine in a cream, ointment, or gel.
Studies in the hematopoietic system disclosed that during endothelial to hematopoietic stem cell transition, ADGRG1 is a transcriptional target of the heptad complex of hematopoietic transcription factors, and is required for hematopoietic cluster formation. Recently, two studies showed that ADGRG1, is a cell autonomous regulator of oligodendrocyte development through Gα12/13 proteins and Rho activation. Della Chiesa et al. demonstrate that ADGRG1 is expressed on CD56dull natural killer (NK) cells. Lin and Hamann's group show all human cytotoxic lymphocytes, including CD56dull NK cells and CD27–CD45RA+ effector-type CD8+ T cells, express ADGRG1.
Protein inhibition by inhibitor binding may induce obstruction in pathway regulation, homeostatic regulation and physiological function. Competitive inhibitors compete with substrate to bind to free enzymes at active sites and thus impede the production of the enzyme-substrate complex upon binding. For example, carbon monoxide poisoning is caused by the competitive binding of carbon monoxide as opposed to oxygen in hemoglobin. Uncompetitive inhibitors, alternatively, bind concurrently with substrate at active sites. Upon binding to an enzyme substrate (ES) complex, an enzyme substrate inhibitor (ESI) complex is formed. Similar to competitive inhibitors, the rate at product formation is decreased also. Lastly, mixed inhibitors are able to bind to both the free enzyme and the enzyme-substrate complex. However, in contrast to competitive and uncompetitive inhibitors, mixed inhibitors bind to the allosteric site. Allosteric binding induces conformational changes that may increase the protein's affinity for substrate. This phenomenon is called positive modulation. Conversely, allosteric binding that decreases the protein's affinity for substrate is negative modulation.
There have been several structures solved for this class of enzymes, given PDB accession codes, and published in peer-reviewed journals. At least 4 such structures have been solved using pig enzymes: PDB: 1OHV, PDB: 1OHW, PDB: 1OHY, PDB: 1SF2, and at least 4 such structures have been solved in Escherichia coli: PDB: 1SFF, PDB: 1SZK, PDB: 1SZS, PDB: 1SZU. There are actually some differences between the enzyme structure for these organisms. E. coli enzymes of GABA-T lack an iron-sulfur cluster that is found in the pig model. Amino acid residues found in the active site of 4-aminobutyrate transaminase include Lys-329, which are found on each of the two subunits of the enzyme. This site will also bind with a pyridoxal 5'- phosphate co-enzyme. Aminooxyacetic acid Gabaculine Phenelzine Phenylethylidenehydrazine (PEH) Rosmarinic acid Valproic acid Vigabatrin 4-Aminobutyrate+Transaminase at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Pearl PL, Parviz M, Hodgeman R, Gibson KM, Reimschisel T (2015). "GABA-transaminase deficiency". MedLink Neurology.
Sources: en.wikipedia.org
PABA is an intermediate in the synthesis of folate by bacteria, plants, and fungi. Many bacteria, including those found in the human intestinal tract such as E. coli, generate PABA from chorismate by the combined action of the enzymes 4-amino-4-deoxychorismate synthase and 4-amino-4-deoxychorismate lyase. Plants produce PABA in their chloroplasts, and store it as a glucose ester (pABA-Glc) in their tissues. The malarial protozoan Plasmodium only make PABA when necessary, preferring to get it from the surroundings if able to. Some bacteria, including a few found in the human microbiome, are unable to make PABA for themselves but can use PABA to make folate. A few are very efficient at the PABA-to-folate conversion despite not making their own PABA. Sulfonamide drugs are structurally similar to PABA, and their antibacterial activity is due to their ability to interfere with the conversion of PABA to folate by the enzyme dihydropteroate synthetase. Thus, bacterial growth is limited through folate deficiency.
Cell shrinkage and rounding occur because of the two parallel processes: (a) retraction of lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases and (b) water removal decreasing cytoplasmic diffusion. The cytoplasm appears dense, and the organelles appear tightly packed. Chromatin undergoes condensation into compact patches against the nuclear envelope (also known as the perinuclear envelope) in a process known as pyknosis, a hallmark of apoptosis. The nuclear envelope becomes discontinuous and the DNA inside it is fragmented in a process referred to as karyorrhexis. The nucleus breaks into several discrete chromatin bodies or nucleosomal units due to the degradation of DNA. Apoptosis progresses quickly and its products are quickly removed, making it difficult to detect or visualize on classical histology sections. During karyorrhexis, endonuclease activation leaves short DNA fragments, regularly spaced in size. These give a characteristic "laddered" appearance on agar gel after electrophoresis. Tests for DNA laddering differentiate apoptosis from ischemic or toxic cell death.
The mechanism of transport for importers supports the alternating-access model. The resting state of importers is inward-facing, where the nucleotide binding domain (NBD) dimer interface is held open by the TMDs and facing outward but occluded from the cytoplasm. Upon docking of the closed, substrate-loaded binding protein towards the periplasmic side of the transmembrane domains, ATP binds and the NBD dimer closes. This switches the resting state of transporter into an outward-facing conformation, in which the TMDs have reoriented to receive substrate from the binding protein. After hydrolysis of ATP, the NBD dimer opens and substrate is released into the cytoplasm. Release of ADP and Pi reverts the transporter into its resting state. The only inconsistency of this mechanism to the ATP-switch model is that the conformation in its resting, nucleotide-free state is different from the expected outward-facing conformation. Although that is the case, the key point is that the NBD does not dimerize unless ATP and binding protein is bound to the transporter.
The iron-containing co-factor is found tightly associated with the protein. It can be released upon denaturation with 2-mercaptoethanol or guanidine hydrochloride. Expression of the Hmd gene in E. coli without the co-factor results in an inactive holoenzyme. However, hydrogenase activity can be rescued by the addition of the iron-containing cofactor taken from denatured active enzyme. As mentioned, irradiation of the cofactor with UV light results in the loss of CO and Fe. In addition the 542 Da compound can be further degraded by a phosphodiesterase (which specifically cleaves phosphate bonds). Hydrolysis of the phosphate bonds generates the ribonucleotide guanosine monophosphate and a modified 2-pyridone. On the basis of spectroscopic characterization, Shima et al. have proposed a structure for this organic cofactor (minus the iron atom and CO molecules) as shown:
While APHL primarily focuses on public health laboratories in the United States, their global health program makes an effort to help other countries strengthen their own laboratory practices.APHL works with more than 30 countries to: Share effective testing procedures Develop laboratory policies Improve the quality of data Train laboratory leaders Utilize information management systems Create strategies to monitor and detect Establish emergency response programs Design training programs APHL also works with public health laboratories around the world to share information on global health crises and promotes cross-border collaboration.
Sources: en.wikipedia.org
April III was defensive quality control coach for the Philadelphia Eagles from 2011 to 2012. In 2013, April III moved to the New York Jets as defensive quality control coach and assistant linebacker coach. In 2014, he was promoted to linebackers coach with the Jets. In 2015, April III moved with Rex Ryan from the Jets to the Buffalo Bills and continued to serve as linebackers coach through 2016. On February 1, 2026, April III returned to the Buffalo Bills as the team's new outside linebackers coach, under head coach Joe Brady. April III had accepted a position to be the defensive ends coach with Minnesota in the college ranks only a month earlier. April earned his bachelor's degree in sports management from Louisiana-Lafayette. He is the son of Bobby April Jr., a former NFL and college special teams coordinator. Buffalo Bills profile Wisconsin profile
Alfred Ellis Wilhelmi (1910–1994) was an American endocrinologist recognized for contributing to the understanding of anterior pituitary hormones. Born in Lakewood, Ohio, Wilhelmi attended Cleveland public schools. Wilhelmi earned a B.S. degree in premedical sciences from Western Reserve University in 1933. He then attended Oxford University as a Rhodes Scholar, where he obtained a B.A. in 1933 and Ph.D. in animal physiology in 1937. He then joined Yale University's Biochemistry Department, rising to the position of Professor in 1950. Wilhelmi chaired the Department of Biochemistry at Emory University School of Medicine from 1950 to 1977. In 1960, he was named Charles Howard Candler Professor of Biochemistry. In 1979, he received Emory's Thomas Jefferson award for service to the university and community. Wilhelmi also was President of the Endocrine Society from 1968 to 1969. During his career, he published over 80 articles in scientific journals.
Adhesion G protein-coupled receptor G1 also known as GPR56 is a protein encoded by the ADGRG1 gene. ADGRG1 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. ADGRG1 is expressed in liver, muscle, tendon, neural, and cytotoxic lymphoid cells in human as well as in hematopoietic precursor, muscle, and developing neural cells in the mouse. ADGRG1 has been shown to have numerous role in cell guidance/adhesion as exemplified by its roles in tumour inhibition and neuron development. More recently it has been shown to be a marker for cytotoxic T cells and a subgroup of Natural killer cells. The ADGRG1 protein binds transglutaminase 2 to suppress tumor metastasis and binds collagen III to regulate cortical development and lamination.
The amino acids that make up a particular helix can be plotted on a helical wheel, a representation that illustrates the orientations of the constituent amino acids (see the article for leucine zipper for such a diagram). Often in globular proteins, as well as in specialized structures such as coiled-coils and leucine zippers, an α-helix will exhibit two "faces" – one containing predominantly hydrophobic amino acids oriented toward the interior of the protein, in the hydrophobic core, and one containing predominantly polar amino acids oriented toward the solvent-exposed surface of the protein. Changes in binding orientation also occur for facially-organized oligopeptides. This pattern is especially common in antimicrobial peptides, and many models have been devised to describe how this relates to their function. Common to many of them is that the hydrophobic face of the antimicrobial peptide forms pores in the plasma membrane after associating with the fatty chains at the membrane core.
Class A (or 1) (Rhodopsin-like) Class B (or 2) (Secretin receptor family) Class C (or 3) (Metabotropic glutamate/pheromone) Class D (or 4) (Fungal mating pheromone receptors) Class E (or 5) (Cyclic AMP receptors) Class F (or 6) (Frizzled/Smoothened) More recently, an alternative classification system called GRAFS (Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B. An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions. Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach. GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
Sources: en.wikipedia.org
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.
No. SR9009 has not been approved as a therapeutic drug in the United States, European Union, or other major markets. Human safety and efficacy data are very limited. Its presence in consumer products does not imply regulatory approval.
The World Anti-Doping Agency lists SR9009 as a prohibited substance because it can alter gene expression and metabolic pathways relevant to performance. The ban applies at all times, not only during competition. Detection relies on laboratory methods such as mass spectrometry.
It is usually detected by LC-MS or HPLC-UV against a reference standard. In biological matrices, metabolite targeting can improve detection. No universal immunoassay is widely available.