REV-ERB agonist 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 2026-03-29 and is reviewed periodically as new material appears.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C20H24ClN3O4S | Reported for the free base |
| Molecular weight | 437.9 g/mol | Calculated from the formula |
| Primary target | REV-ERBα and REV-ERBβ | Nuclear receptors involved in circadian regulation |
| Solubility | Soluble in DMSO and ethanol | Poorly soluble in water |
| Typical storage | -20 °C, desiccated | Protect from light and moisture |
Laboratory studies often administer SR9009 by injection because oral absorption appears poor in rodents. Reported pharmacokinetic properties include rapid metabolism and low systemic exposure after oral dosing. Human pharmacokinetic data are sparse, so absorption, distribution, metabolism, and excretion in people are not well defined. Some research explores related REV-ERB compounds with improved drug-like properties. Regulatory approval for any REV-ERB agonist as a human medicine has not been granted to date.
SR9009 is a synthetic small molecule studied as an agonist of the nuclear receptors REV-ERBα and REV-ERBβ, also called NR1D1 and NR1D2. These receptors help regulate circadian rhythms and metabolic gene programs. The compound was developed for laboratory research, not as an approved therapeutic. Its identity is distinct from steroid hormones and selective androgen receptor modulators. Scientific interest centers on how REV-ERB activation changes gene expression in cells and animal models.
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. These receptors help regulate circadian rhythms and metabolic gene expression. In laboratory experiments, SR9009 binds these receptors and alters transcription of genes involved in lipid handling, glucose metabolism, and mitochondrial function. It is not a naturally occurring compound and has no approved therapeutic use. Research interest stems from its ability to modify energy metabolism in cells and animal models.
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.
Substitution of the poly-Pro II (φ,ψ) dihedral angles into this equation yields almost exactly Ω = -120°, i.e., the PPII helix is a left-handed helix (since Ω is negative) with three residues per turn (360°/120° = 3). The rise per residue is approximately 3.1 Å. This structure is somewhat similar to that adopted in the fibrous protein collagen, which is composed mainly of proline, hydroxyproline, and glycine. PPII helices are specifically bound by SH3 domains; this binding is important for many protein-protein interactions and even for interactions between the domains of a single protein. The PPII helix is relatively open and has no internal hydrogen bonding, as opposed to the more common helical secondary structures, the alpha helix and its relatives the 310 helix and the pi helix, as well as the β-helix. The amide nitrogen and oxygen atoms are too far apart (approximately 3.8 Å) and oriented incorrectly for hydrogen bonding. Moreover, these atoms are both H-bond acceptors in proline; there is no H-bond donor due to the cyclic side chain. The PPII backbone dihedral angles (-75°, 150°) are observed frequently in proteins, even for amino acids other than proline. The Ramachandran plot is highly populated in the PPII region, comparably to the beta sheet region around (-135°, 135°). For example, the PPII backbone dihedral angles are often observed in turns, most commonly in the first residue of a type II β-turn. The "mirror image" PPII backbone dihedral angles (75°, -150°) are rarely seen, except in polymers of the achiral amino acid glycine.
=== Cystic fibrosis === Cystic fibrosis affects pancreatic ducts as well as many other secretory epithelia. Cystic fibrosis transmembrane conductance regulator (CFTR) is the mutated gene and is essential to chloride and bicarbonate secretion. The abnormal amount of anion secretion causes a reduced amount of ductal water flow. Because of this, the duct's protein concentration increases and causes the duct lumina to get plugged. The onset of cystic fibrosis affects the pancreas more than any other organ (even before birth).
== General readings == Cross, J.W. (2006). The Charms of Duckweed. Landolt, E. (1986) Biosystematic investigations in the family of duckweeds (Lemnaceae). Vol. 2. The family of Lemnaceae – A monographic study. Part 1 of the monograph: Morphology; karyology; ecology; geographic distribution; systematic position; nomenclature; descriptions. Veröff. Geobot. Inst., Stiftung Rübel, ETH, Zurich.
Oligonucleotides are chemically synthesized using building blocks, protected phosphoramidites of natural or chemically modified nucleosides or, to a lesser extent, of non-nucleosidic compounds. The oligonucleotide chain assembly proceeds in the 3' to 5' direction by following a routine procedure referred to as a "synthetic cycle". Completion of a single synthetic cycle results in the addition of one nucleotide residue to the growing chain. A less than 100% yield of each synthetic step and the occurrence of side reactions set practical limits of the efficiency of the process. In general, oligonucleotide sequences are usually short (13–25 nucleotides long). The maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide residues. HPLC and other methods can be used to isolate products with the desired sequence.
=== Recurring or guest === Avantika Vandanapu as Ophelia, a young advanced witch Madelaine Petsch as Kira, Ben's girlfriend Elle Chapman as Ashley, one of Kira's friends Berto Colón as Joe the Doorman Fedor Steer as Mr. Nas, an elderly gentleman being cared for by Constance and Ben John Waters as Mr. Phibes, a mysterious phlebotomist John Carroll Lynch as Twisty the Clown, a disgraced clown and a serial killer, reprising his role from Freak Show and Cult Tig Notaro as Ricochet, a clown school teacher Jamie Brewer as: Adelaide Langdon, Constance's daughter, reprising her role from Murder House Nan, a witch, reprising her role from Coven and Apocalypse Mena Suvari as Elizabeth Short, a ghost of an aspiring actress, reprising her role from Murder House and Apocalypse Paul Anthony Kelly as young Nas Mat Fraser as Paul the Illustrated Seal, a freak show member with phocomelia, reprising his role from Freak Show Orlando Jones as Papa Legba, a gatekeeper of the spirit world; Jones replaces Lance Reddick, who portrayed Papa Legba in Coven and Apocalypse Seth Gabel as Jeffrey Dahmer, a serial killer, reprising his role from Hotel Zach Villa as Richard Ramirez, a serial killer, reprising his role from 1984 Alex Consani as Morwenna Grace Dumdaw Cara Delevingne Charlie Carver
Sources: en.wikipedia.org
== Structure == Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. The subdesignation α1, α2, etc. refers to separate domains within the HLA gene; each domain is usually encoded by a different exon within the gene, and some genes have further domains that encode leader sequences, transmembrane sequences, etc. These molecules have both extracellular regions as well as a transmembrane sequence and a cytoplasmic tail. The α1 and β1 regions of the chains come together to make a membrane-distal peptide-binding domain, while the α2 and β2 regions, the remaining extracellular parts of the chains, form a membrane-proximal immunoglobulin-like domain. The antigen binding groove, where the antigen or peptide binds, is made up of two α-helixes walls and β-sheet. Because the antigen-binding groove of MHC class II molecules is open at both ends while the corresponding groove on class I molecules is closed at each end, the antigens presented by MHC class II molecules are longer, generally between 15 and 24 amino acid residues long.
=== Sclerostin === Osteocytes synthesize sclerostin, a secreted protein that inhibits bone formation by binding to LRP5/LRP6 coreceptors and blunting Wnt signaling. Sclerostin, the product of the SOST gene, is the first mediator of communication between osteocytes, bone forming osteoblasts and bone resorbing osteoclasts, critical for bone remodeling. Only osteocytes express sclerostin, which acts in a paracrine fashion to inhibit bone formation. Sclerostin is inhibited by parathyroid hormone (PTH) and mechanical loading. Sclerostin antagonizes the activity of BMP (bone morphogenetic protein), a cytokine that induces bone and cartilage formation.
=== Ocular hypertension === Ocular hypertension (increased pressure within the eye) is an important risk factor for glaucoma, but only about 10–70% of people, depending on ethnic group, with primary open-angle glaucoma actually have elevated ocular pressure. Ocular hypertension—an intraocular pressure above the traditional threshold of 21 mmHg (28 hPa) or even above 24 mmHg (32 hPa)—is not necessarily a pathological condition, but it increases the risk of developing glaucoma. A study with 1636 persons aged 40–80 who had an intraocular pressure above 24 mmHg in at least one eye, but no indications of eye damages, showed that after five years, 9.5% of the untreated participants and 4.4% of the treated participants had developed glaucomatous symptoms, meaning that only about one in 10 untreated people with elevated intraocular pressure will develop glaucomatous symptoms over that period. Given these results, the clinical decision to treat everyone with elevated intraocular pressure with glaucoma therapy as a preventative measure is a matter of debate. As of 2018, most ophthalmologists favored treatment of those with additional risk factors. For eye pressures, a value of 28 hPa (21 mmHg) above atmospheric pressure 1,010 hPa (760 mmHg) is often used, with higher pressures leading to a greater risk. However, some may have high eye pressure for years and never develop damage. Conversely, optic nerve damage may occur with normal pressure, known as normal-tension glaucoma.
=== Biosynthesis === HMB is synthesized in the human body through the metabolism of L-leucine, a branched-chain amino acid. In healthy individuals, approximately 60% of dietary L-leucine is metabolized after several hours, with roughly 5% (2–10% range) of dietary L-leucine being converted to HMB.
== Contraindications and precautions == Patients with known hypersensitivity to Oprelvekin itself or any other ingredient. Patients with severe or decompensated heart failure should not be treated, because Oprelvekin may cause excessive fluid retention with edema and cardiac decompensation. Patients with compensated heart disease should be treated with caution and under permanent clinical supervision. Neumega is not indicated following myeloablative chemotherapy (increased likelihood of severe side-effects) and in pediatric patients. Renal impairment: Neumega is excreted renally. No differences of pharmakinetic parameters and clinical differences have been seen in mild to moderate impairment. Severe impairment has led to an increased number of patients with reduced hemoglobin due to dilutional anemia. Patients with severely disturbed renal function should be monitored very closely. The efficacy of Oprelvekin has not been systematically studied in patients receiving chemotherapy regimes of more than 5 days duration/each cycle or in those regimes containing agents that induce delayed thrombocytopenia (e.g. nitrosoureas, mitomycin C. Neumega should not be given in these cases.
Sources: en.wikipedia.org
It is a synthetic REV-ERB agonist used mainly in preclinical research. It is not an approved medicine for human use.
It binds to REV-ERBα and REV-ERBβ, nuclear receptors involved in circadian and metabolic gene regulation. This can alter transcription of genes related to lipid and glucose metabolism in experimental models.
No controlled human trials have established that effect. Endurance findings come primarily from rodent studies, and human responses remain unknown.
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.