This is a working overview of REV-ERB, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-01-02. Anything still debated is marked as such rather than presented as settled.
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 developed as a REV-ERB agonist. It binds to REV-ERBα and REV-ERBβ, nuclear receptors that help regulate circadian rhythms and metabolic gene expression. In cell and animal studies, the compound alters lipid and glucose handling and influences skeletal muscle oxidative capacity. Its exact effects in humans remain largely uncharacterized because controlled clinical trials have not been reported. The molecule is frequently described in preclinical literature as a metabolic modulator.
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.
| 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. |
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.
At the molecular level, SR9009 binds the ligand-binding domain of REV-ERB and strengthens recruitment of corepressor proteins such as NCoR and HDAC3. This increases repression of target genes, including Bmal1 and other clock-controlled and metabolic genes. In rodent studies, such changes have been linked to altered lipid handling, glucose metabolism, and energy expenditure. The precise chain of events between receptor binding and whole-body effects remains an active area of research. Findings in animals do not automatically translate to humans.
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. 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.
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.
== Function == Citrulline is a metabolic intermediate within the urea cycle, which is the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase. In the yeast species Saccharomyces cerevisiae, citrulline is a metabolic intermediate in the latter, cytosolic half of the arginine biosynthesis pathway. Several proteins contain citrulline as a result of a post-translational modification. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases, which convert arginine into citrulline in a process called citrullination or deimination with the help of calcium ions. Proteins that normally contain citrulline residues include myelin basic protein, filaggrin, and several histone proteins, whereas other proteins, such as fibrin and vimentin are susceptible to citrullination during cell death and tissue inflammation. Circulating citrulline concentration is a biomarker of intestinal functionality.
=== Pharmacomicrobiomics === The human metagenome (i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals. Since the total number of microbial and viral cells in the human body (over 100 trillion) greatly outnumbers human cells (tens of trillions), there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the human microbiome, drug metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a drug's clinical efficacy and toxicity profile. The field that studies these interactions is known as pharmacomicrobiomics. Similar to most biomolecules and other orally administered xenobiotics (i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by human gastrointestinal microbiota (primarily bacteria) prior to absorption into the blood stream. The first amphetamine-metabolizing microbial enzyme, tyramine oxidase from a strain of E. coli commonly found in the human gut, was identified in 2019. This enzyme was found to metabolize amphetamine, tyramine, and phenethylamine with roughly the same binding affinity for all three compounds.
The history of the mole is intertwined with that of units of molecular mass, and the Avogadro constant. The first table of standard atomic weight was published by John Dalton (1766–1844) in 1805, based on a system in which the relative atomic mass of hydrogen was defined as 1. These relative atomic masses were based on the stoichiometric proportions of chemical reaction and compounds, a fact that greatly aided their acceptance; it was not necessary for a chemist to subscribe to atomic theory (which was not universally accepted at the time) to make practical use of the tables. This would lead to some confusion between atomic masses (promoted by proponents of atomic theory) and equivalent weights (promoted by its opponents and which sometimes differed from relative atomic masses by an integer factor), which would last throughout much of the nineteenth century. Jöns Jacob Berzelius (1779–1848) was instrumental in the determination of relative atomic masses to ever-increasing accuracy. He was also the first chemist to use oxygen as the standard to which other masses were referred. Oxygen is a useful standard, as, unlike hydrogen, it forms compounds with most other elements, especially metals. However, he chose to fix the atomic mass of oxygen as 100, which did not catch on. Charles Frédéric Gerhardt (1816–56), Henri Victor Regnault (1810–78) and Stanislao Cannizzaro (1826–1910) expanded on Berzelius' works, resolving many of the problems of unknown stoichiometry of compounds, and the use of atomic masses attracted a large consensus by the time of the Karlsruhe Congress (1860).
Sources: en.wikipedia.org
OD600 (Also written as O.D. 600, D600, o.d. 600, OD600) is an abbreviation indicating the optical density of a sample measured at a wavelength of 600 nm in 1 cm light path (unless otherwise stated). It is a commonly used in microbiology for estimating the concentration of bacteria or other cells in a liquid as the 600 nm wavelength does little to damage or hinder their growth. OD600 is a type of turbidity measurement. Since optical density in case of OD600 measurements results from light scattering by particles (cells) rather than absorption, size and shape as well as dead cells and debris of a cell may add to light dissipating. Distinctive cell types that are at densities of the same level (eg. cell/mL), may, therefore, show varying values OD600, when estimated on a similar instrument. For turbid samples such as cell cultures, the major contributor for the optical density measured is light scattering and not the result of molecular absorption following the Beer-Lambert Law. The measurements are therefore depending on the optical setup of the spectrophotometer (distance between the cell holder and instrument exit slit, monochromator optics, slit geometry, etc.), different instrument types will most likely tend to give different OD600 readings for the same turbid sample. Measuring the change of the OD600 as a function of time (e.g. measuring of the growth curve) may indicate the growth phase of cultured cell population, i.e. whether it is in the lag phase, log phase, or stationary phase.
Finally, if an employer is insolvent, at common law the insolvency terminates contracts on reasonable notice. To protect pay, under the Fair Entitlements Guarantee Act 2012 the federal government has a scheme for payments to employees whose wages are not otherwise covered.
Bavington, Dean L. Y. Managed Annihilation: An Unnatural History of the Newfoundland Cod Collapse (University of British Columbia Press; 2010) 224 pages. Links the collapse of Newfoundland and Labrador cod fishing to state management of the resource. Cobb, John N. (1916). Pacific Cod Fisheries. Bureau of Fisheries Document. Vol. 830. Washington, DC: Government Printing Office. OCLC 14263968. Greenberg, Paul (2010). Four Fish: The Future of the Last Wild Food. New York: Penguin Press. ISBN 978-1-59420-256-8. OCLC 813929026. Mark Kurlansky (1997). Cod: A Biography of the Fish That Changed the World. Shields, Edward (2001). Salt of the Sea: The Pacific Coast Cod Fishery and the Last Days of Sail. Lopez Island, Wash.: Heritage House. ISBN 978-1-894384-35-3.
Sources: en.wikipedia.org
=== Insulin effects on strength and exercise performance === Exogenous insulin significantly boosts the rate of glucose metabolism in training athletes along with a substantial increase in the peak V̇O2. Insulin is thought to enhance performance by increasing protein synthesis, reducing protein catabolism, and facilitating the transfer of certain amino acids in human skeletal muscle. Insulin-treated athletes are perceived to have lean body mass because physiological hyperinsulinemia in human skeletal muscle improves the activity of amino acid transport, which in turn promotes protein synthesis. Insulin stimulates the transport of amino acids into cells and also controls glucose metabolism. It decreases lipolysis and increases lipogenesis which is why bodybuilders and athletes use rhGH in conjunction with it as to offset this negative effect while maximizing protein synthesis. The athletes extrapolated the physiology of the diabetic patient in the sporting arena because they are interested in the suppression of proteolysis. Insulin administration is found to be protein anabolic in the insulin-resistant state of chronic renal failure. It inhibits proteolysis and when administered along with amino acids, it enhances net protein synthesis. Exogenous insulin injection creates an in-vivo hyperinsulinemic clamp, boosting muscle glycogen before and during the recovery phases of intense exercise. Power, strength, and stamina are all expected to increase as a result, and it might also speed up the healing process after intense physical activity.
In neurons that use DA as the transmitter, the decarboxylation of L-DOPA to dopamine is the final step in formation of the transmitter; however, in those neurons using norepinephrine (noradrenaline) or epinephrine (adrenaline) as transmitters, the enzyme dopamine β-hydroxylase (DBH), which converts dopamine to yield norepinephrine, is also present. In still other neurons in which epinephrine is the transmitter, a third enzyme phenylethanolamine N-methyltransferase (PNMT) converts norepinephrine into epinephrine. Thus, a cell that uses epinephrine as its transmitter contains four enzymes (TH, AADC, DBH, and PNMT), whereas norepinephrine neurons contain only three enzymes (lacking PNMT) and dopamine cells only two (TH and AADC).
Communication satellite – an artificial satellite used as a telecommunications relay to transmit data between widely separated points on Earth. These are used because the microwaves used for telecommunications travel by line of sight and so cannot propagate around the curve of the Earth. As of 1 January 2021, there were 2,224 communications satellites in Earth orbit. Most are in geostationary orbit 22,200 miles (35,700 km) above the equator, so that the satellite appears stationary at the same point in the sky, so the satellite dish antennas of ground stations can be aimed permanently at that spot and do not have to move to track it. In a satellite ground station a microwave transmitter and large satellite dish antenna transmit a microwave uplink beam to the satellite. The uplink signal carries many channels of telecommunications traffic, such as long-distance telephone calls, television programs, and internet signals, using a technique called frequency-division multiplexing (FDM). On the satellite, a transponder receives the signal, translates it to a different downlink frequency to avoid interfering with the uplink signal, and retransmits it down to another ground station, which may be widely separated from the first. There the downlink signal is demodulated and the telecommunications traffic it carries is sent to its local destinations through landlines. Communication satellites typically have several dozen transponders on different frequencies, which are leased by different users.
ribonuclease (RNase) Any of a class of nuclease enzymes which catalyze the hydrolytic cleavage of phosphodiester bonds in RNA molecules, thus severing polymeric strands of ribonucleotides into smaller components. Compare deoxyribonuclease.
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.
It is a synthetic REV-ERB agonist used mainly in preclinical research. It is not an approved medicine for human use.