If you have been reading about NR1D1 and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-02-20. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
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.
| 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 binds REV-ERB receptors and alters their repressive activity on target genes. This action can change transcription of genes involved in lipid handling, glucose metabolism, and mitochondrial function. In rodent studies, treated animals have shown changes in muscle oxidative capacity and exercise performance, though effects vary by dose, duration, and model. The precise molecular steps connecting receptor binding to whole-body outcomes are still an active area of investigation. Findings in animals do not automatically translate to humans.
Because REV-ERB receptors are core clock components, SR9009 has been examined for effects on daily rhythms as well as metabolism. Research has explored whether the compound can shift or reinforce circadian gene expression in tissues such as liver and muscle. Some studies report improved metabolic markers in obese or diabetic mice, while others show context-dependent responses. Questions remain about which effects are direct, which are secondary to timing, and how they might differ across species.
Analytical methods for SR9009 typically rely on liquid chromatography coupled with tandem mass spectrometry. The technique can separate the parent compound from related substances and detect low concentrations in biological matrices. Urine and blood are common samples in anti-doping testing, while in vitro studies may use cell culture media. Rapid metabolism and low expected concentrations make method validation important for reliable identification. Exact metabolite patterns can vary by species and are not fully mapped.
Regulatory treatment of SR9009 reflects its investigational status. The compound has no approved human therapeutic indication, and sports authorities prohibit its use. It appears on anti-doping lists as a non-approved substance or metabolic modulator, depending on the list version. Products sold online as research chemicals are not quality-controlled medicines, so their identity and purity can differ from the label. Such products may also contain unlisted compounds, which complicates both testing and safety assessment.
Scientific discussion of SR9009 often separates animal evidence from human anecdote. Rodent studies provide controlled data on endurance, metabolism, and gene expression, but they use specific strains, doses, and treatment durations. Human reports are mostly uncontrolled and cannot establish cause and effect. Open questions include oral bioavailability, tissue distribution, metabolic stability, and long-term effects. Review articles generally call for more rigorous pharmacokinetic and safety research before any clinical use could be considered.
Detection of SR9009 in biological samples usually relies on liquid chromatography coupled to tandem mass spectrometry. This approach separates the compound from matrix components and identifies it by mass transitions. Because SR9009 can undergo metabolism, laboratories often look for both parent drug and specific metabolites. Sample preparation may involve protein precipitation or solid-phase extraction. Method validation examines sensitivity, carryover, and interference from related substances, and reference standards are required for accurate calibration.
Storage recommendations for SR9009 reference material typically specify a freezer at -20 °C or lower, with protection from moisture and light. Repeated freeze-thaw cycles can degrade small molecules and introduce variability. Stock solutions in dimethyl sulfoxide are often aliquoted to avoid repeated handling. Stability studies may examine degradation under heat, humidity, and light exposure. The compound's thiophene and nitro groups can participate in reactions that alter analytical signals over time, so such changes affect quantitative results.
Quality control for research materials includes identity confirmation by nuclear magnetic resonance and purity assessment by high-performance liquid chromatography. Mass spectrometry provides molecular weight confirmation and can detect related impurities. Purchasers should request a certificate of analysis that lists lot-specific data. Online products advertised for human use often lack such documentation. Distinguishing legitimate research material from mislabeled or contaminated samples is a recurring challenge in independent testing, and independent laboratories may use orthogonal methods to verify identity.
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.
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.
===== Proposed ===== Despite its superiority to current methods of large-surface-area wound care—gauze wrapping, honey vinegar treatments, and systemic antibiotics—and popular dermal patch uses, spider silk has not found its way into clinical practice. Historically the main reason for this is the difficulty of farming, and harvesting the silk. Unlike silkworms, that spin silk for several easy-to-replicate conditions, spiders spin silk for specific purposes such as catching prey, difficult to replicate in laboratory conditions. In addition, spiders generally tend to be cannibalistic, so breeding sufficient numbers becomes difficult. Forced silking yields unsuitable silks. The most popular proposed use case for dermal applications are:
Computational Resources for Drug Discovery (CRDD) is an important module of the in silico module of Open Source for Drug Discovery (OSDD). The CRDD web portal provides computer resources related to drug discovery, predicting inhibitors, and predicting the ADME-Tox properties of molecules on a single platform. It caters to researchers researching computer-aided drug design by providing computational resources, and hosting a discussion forum. One of the major objectives of CRDD is to promote open source software in the field of cheminformatics and pharmacoinformatics.
==== Hormones ==== BST is destroyed in the digestive system and even if directly injected, has not been found to have any direct effect on humans. Researchers have found that "IGF-1 in milk is not denatured by pasteurization and the extent to which intact, active IGF-1 is absorbed through the human digestive tract remains still however uncertain" implicating that an extensive study on the nature of IGF-1 in relation to rBST milk is required. FDA rBST labeling guidelines state, "FDA is concerned that the term 'rBST free' may imply a compositional difference between milk from treated and untreated cows rather than a difference in the way the milk is produced. Without proper context, such statements could be misleading. Such unqualified statements may imply that milk from untreated cows is safer or of higher quality than milk from treated cows. Such an implication would be false and misleading". The FDA has determined that no significant difference has been shown between milk derived from rBST treated and non-rBST treated cows. The FDA, World Health Organization, and National Institutes of Health have independently stated that dairy products and meat from rBST-treated cows are safe for human consumption. The American Cancer Society issued a report declaring, "The evidence for potential harm to humans [from rBGH milk] is inconclusive. It is not clear that drinking milk produced using rBGH significantly increases IGF-1 levels in humans or adds to the risk of developing cancer. More research is needed to help better address these concerns."
Sources: en.wikipedia.org
Merigolix (INNTooltip International Nonproprietary Name; developmental code names HS-10518, NCE-403, SKI-2670, TU-2670) is a gonadotropin releasing hormone (GnRH) antagonist which is under development for the treatment of endometriosis and uterine fibroids. It is taken by mouth. The drug is being developed by TiumBio, Daewon Pharmaceutical, and Jiangsu Hansoh Pharmaceutical. As of October 2024, it is in phase 2 clinical trials for both endometriosis and uterine fibroids.
Prolactin-releasing hormone, also known as PRLH, is a hypothetical human hormone or hormone releasing factor. Existence of this factor has been hypothesized as prolactin is the only currently known hormone for which almost exclusively negative regulating factors are known (such as dopamine, leukemia inhibitory factor, some prostaglandins) but few stimulating factor. Its secretion is mediated by estrogen from placenta during pregnancy to elevate blood level of prolactin. While many prolactin stimulating and enhancing factors are well known (such as thyrotropin-releasing hormone, oxytocin, vasoactive intestinal peptide and estrogen) those have primary functions other than stimulating prolactin release and the search for hypothetical releasing factor or factors continues. The prolactin-releasing peptide identified in 1998 was a candidate for this function, however as of 2008 it appears its function is not yet completely elucidated.
=== Active funds === A few actively managed investment funds have been created which target the megacap segment of the US stock market. They explicitly give their own definitions of the megacap segment when explaining their investment strategies. The Fidelity Mega Cap Stock Fund mutual fund (ticker symbol: FGRTX) defines megacaps as companies "whose market capitalization is similar to [that] of companies in the Russell Top 200 Index or the S&P 100 Index". As of December 31, 2025, the fund had 116 holdings. The Principal US Mega-Cap ETF (Nasdaq: USMC) defines megacaps as companies "with market capitalizations in the top 50th percentile of the S&P 500 Index". As of September 30, 2025, such companies had market caps ranging from $149.6 billion to $4.6 trillion. As of June 30, 2025, the fund had 27 holdings.
=== Connection with Cancer treatment === hCTR1 is upregulated in various cancer types, and it's associated with prognosis in several solid tumors. Atox1 and ATP7B were found to be important for Pt-based drug resistance. hCTR1 plays a role in oncology, hCTR1 facilitates uptake of platinum-based chemotherapeutic agents, such as cisplatin. Yeast and mammalian cells lacking CTR1 were resistant to cisplatin, while cells overexpressing CTR1 accumulated more of the drug. Tumor cells when exposed to cisplatin often react by increased degradation of hCTR1, thereby they become drug-resistant while simultaneously exhibiting signs of perturbed copper homeostasis. Studies of Atox1 in cancer cells demonstrated that this copper chaperone is crucial for cancer cell proliferation and survival. Small molecules targeting Atox1 have been proved to effectively block Cu-trafficking. For that reason reduce cell proliferation in lung, leukemia, breast, head, and neck cancer cell lines by elevating cellular ROS levels and reducing cellular NADPH and GSH levels. In contrast, healthy cells were barely affected by these small molecules.
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 research compound that activates REV-ERB nuclear receptors. It is not an approved drug or dietary supplement. Most information comes from cell and animal studies.