LC-MS/MS raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
Reviewed 2025-08-11. Anything still debated is marked as such rather than presented as settled.
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.
At the molecular level, SR9009 binds REV-ERBα and REV-ERBβ and alters their repressive activity on target genes. These nuclear receptors help regulate the circadian clock, lipid synthesis, glucose metabolism, and inflammatory pathways. By changing transcription, the compound can shift the timing or magnitude of downstream metabolic processes in model systems. It does not act through androgen receptors or adenosine receptors, which distinguishes it from several substances sold for athletic performance. Whether the same transcriptional changes occur in humans at tolerable exposures remains an open question because controlled human studies are lacking.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C20H24ClN3O4S | Derived from published structure. |
| Molecular weight | 437.94 g/mol | Calculated value. |
| Appearance | White to off-white solid | Typical for purified research samples. |
| Solubility | DMSO, ethanol; low in water | Class: poorly water-soluble. |
| Typical storage | -20 °C, desiccated, protected from light | Limits degradation. |
Laboratory identification of SR9009 typically relies on chromatographic separation coupled to mass spectrometry, often with ultraviolet detection as a secondary check. Nuclear magnetic resonance spectroscopy can confirm molecular structure when a reference standard is available. Because many suppliers sell the compound as a research chemical, independent identity testing is important for experimental reproducibility. A single retention time is not sufficient proof of identity, especially when related compounds may be present. Purity assessments usually report a percentage based on area normalization.
SR9009 is generally described as poorly soluble in water and more soluble in organic solvents such as dimethyl sulfoxide and ethanol. Stock solutions are commonly prepared in an organic solvent before dilution into an aqueous buffer or vehicle. Precipitation can occur if the organic fraction is reduced too quickly or if the final concentration exceeds the compound's solubility limit. Sonication or gentle warming may aid dissolution in some protocols, but excessive heat can promote degradation. Container material and pH can also influence observed solubility.
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.
The tournament will be hosted by whoever wins the regular season title. Right now, either James Madison or Old Dominion will host the tournament, depending on their regular season outcomes. Last updated: October 31, 2011Source: NMN Athletics Colonial Athletic Association 2011 CAA Men's Soccer Tournament 2011 NCAA Division I men's soccer season 2011 NCAA Division I Men's Soccer Championship
Nevertheless, the resistance of extracellular matrix proteins to proteolysis renders their advanced glycation end products less conducive to being eliminated. While the AGE free adducts are released directly into the urine, AGE peptides are endocytosed by the epithelial cells of the proximal tubule and then degraded by the endolysosomal system to produce AGE amino acids. It is thought that these acids are then returned to the kidney's inside space, or lumen, for excretion. AGE free adducts are the major form through which AGEs are excreted in urine, with AGE-peptides occurring to a lesser extent but accumulating in the plasma of patients with chronic kidney failure. Larger, extracellularly derived AGE proteins cannot pass through the basement membrane of the renal corpuscle and must first be degraded into AGE peptides and AGE free adducts. Peripheral macrophage as well as liver sinusoidal endothelial cells and Kupffer cells have been implicated in this process, although the real-life involvement of the liver has been disputed.
Large AGE proteins unable to enter the Bowman's capsule are capable of binding to receptors on endothelial and mesangial cells and to the mesangial matrix. Activation of RAGE induces production of a variety of cytokines, including TNFβ, which mediates an inhibition of metalloproteinase and increases production of mesangial matrix, leading to glomerulosclerosis and decreasing kidney function in patients with unusually high AGE levels. Peptides and free adducts, the only breakdown products of AGE that are suitable for urinary excretion, are more aggressive than the AGE proteins from which they are derived, and they can perpetuate related pathology in people with diabetes, even after hyperglycemia has been brought under control.
Sources: en.wikipedia.org
RANKL is a member of the TNF superfamily of ligands. Through binding to the RANK receptor it activates various molecules, like NF-kappa B, MAPK, NFAT and PI3K52. The RANKL/RANK signaling pathway regulates osteoclastogenesis, as well as, the survival and activation of osteoclasts. Adenosine is very relevant in bone metabolism, as it plays a role in formation and activation of both osteoclasts and osteoblasts. Adenosine acts by binding to purinergic receptors and influencing adenylyl cyclase activity and the formation of cAMP and PKA 54. Adenosine may have opposite effects on bone metabolism, because while certain purinergic receptors stimulate adenylyl cyclase activity, others have the opposite effect. Under certain circumstances adenosine stimulates bone destruction and in other situations it promotes bone formation, depending on the purinergic receptor that is being activated.
The first class of adenylyl cyclases occur in many bacteria including E. coli (as CyaA P00936 [unrelated to the Class II enzyme]). This was the first class of AC to be characterized. It was observed that E. coli deprived of glucose produce cAMP that serves as an internal signal to activate expression of genes for importing and metabolizing other sugars. cAMP exerts this effect by binding the transcription factor CRP, also known as CAP. Class I AC's are large cytosolic enzymes (~100 kDa) with a large regulatory domain (~50 kDa) that indirectly senses glucose levels. As of 2012, no crystal structure is available for class I AC. Some indirect structural information is available for this class. It is known that the N-terminal half is the catalytic portion, and that it requires two Mg2+ ions. S103, S113, D114, D116 and W118 are the five absolutely essential residues. The class I catalytic domain (Pfam PF12633) belongs to the same superfamily (Pfam CL0260) as the palm domain of DNA polymerase beta (Pfam PF18765). Aligning its sequence onto the structure onto a related archaeal CCA tRNA nucleotidyltransferase (PDB: 1R89) allows for assignment of the residues to specific functions: γ-phosphate binding, structural stabilization, DxD motif for metal ion binding, and finally ribose binding.
Amyloid is formed through the polymerization of hundreds to thousands of monomeric peptides or proteins into long fibers. Amyloid formation involves a lag phase (also called nucleation phase), an exponential phase (also called growth phase) and a plateau phase (also called saturation phase), as shown in the figure. When the quantity of fibrils is plotted versus time, a sigmoidal time course is observed reflecting the three distinct phases. In the simplest model of 'nucleated polymerization' (marked by red arrows in the figure below), individual unfolded or partially unfolded polypeptide chains (monomers) convert into a nucleus (monomer or oligomer) via a thermodynamically unfavourable process that occurs early in the lag phase. Fibrils grow subsequently from these nuclei through the addition of monomers in the exponential phase. A different model, called 'nucleated conformational conversion' and marked by blue arrows in the figure below, was introduced later on to fit some experimental observations: monomers have often been found to convert rapidly into misfolded and highly disorganized oligomers distinct from nuclei. Only later on, will these aggregates reorganise structurally into nuclei, on which other disorganised oligomers will add and reorganise through a templating or induced-fit mechanism (this 'nucleated conformational conversion' model), eventually forming fibrils.
Sources: en.wikipedia.org
ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) is a laboratory technique used in molecular biology to assess genome-wide chromatin accessibility. The technique was introduced in 2013 by the labs of Will Greenleaf and Howard Chang at Stanford University as an alternative to MNase-seq, FAIRE-Seq and DNase-Seq with faster turnaround time, simpler protocol, and lower DNA input requirements.
A helix has an overall dipole moment due to the aggregate effect of the individual microdipoles from the carbonyl groups of the peptide bond pointing along the helix axis. The effects of this macrodipole are a matter of some controversy. α-helices often occur with the N-terminal end bound by a negatively charged group, sometimes an amino acid side chain such as glutamate or aspartate, or sometimes a phosphate ion. Some regard the helix macrodipole as interacting electrostatically with such groups. Others feel that this is misleading and it is more realistic to say that the hydrogen bond potential of the free NH groups at the N-terminus of an α-helix can be satisfied by hydrogen bonding; this can also be regarded as set of interactions between local microdipoles such as C=O···H−N.
RANKL is a member of the TNF superfamily of ligands. Through binding to the RANK receptor it activates various molecules, like NF-kappa B, MAPK, NFAT and PI3K52. The RANKL/RANK signaling pathway regulates osteoclastogenesis, as well as, the survival and activation of osteoclasts. Adenosine is very relevant in bone metabolism, as it plays a role in formation and activation of both osteoclasts and osteoblasts. Adenosine acts by binding to purinergic receptors and influencing adenylyl cyclase activity and the formation of cAMP and PKA 54. Adenosine may have opposite effects on bone metabolism, because while certain purinergic receptors stimulate adenylyl cyclase activity, others have the opposite effect. Under certain circumstances adenosine stimulates bone destruction and in other situations it promotes bone formation, depending on the purinergic receptor that is being activated.
H3A (aq) + H2O (l) ⇌ H3O+ (aq) + H2A− (aq) Ka1 H2A− (aq) + H2O (l) ⇌ H3O+ (aq) + HA2− (aq) Ka2 HA2− (aq) + H2O (l) ⇌ H3O+ (aq) + A3− (aq) Ka3 An inorganic example of a triprotic acid is orthophosphoric acid (H3PO4), usually just called phosphoric acid. All three protons can be successively lost to yield H2PO−4, then HPO2−4, and finally PO3−4, the orthophosphate ion, usually just called phosphate. Even though the positions of the three protons on the original phosphoric acid molecule are equivalent, the successive Ka values differ since it is energetically less favorable to lose a proton if the conjugate base is more negatively charged. An organic example of a triprotic acid is citric acid, which can successively lose three protons to finally form the citrate ion. Although the subsequent loss of each hydrogen ion is less favorable, all of the conjugate bases are present in solution. The fractional concentration, α (alpha), for each species can be calculated. For example, a generic diprotic acid will generate 3 species in solution: H2A, HA−, and A2−. The fractional concentrations can be calculated as below when given either the pH (which can be converted to the [H+]) or the concentrations of the acid with all its conjugate bases:
Sources: en.wikipedia.org
SR9009 is a synthetic REV-ERB agonist used in laboratory research. It is not an approved drug, and its effects in humans are not well characterized. It is often sold as a research chemical under the name Stenabolic.
No. SR9009 targets the nuclear receptors REV-ERBα and REV-ERBβ, not the androgen receptor. This mechanism differs from selective androgen receptor modulators and from exercise mimetics that act on PPARδ.
Published evidence is mainly preclinical, using cell cultures and animal models. Controlled human trials are not well documented in the public literature. Claims about human performance or health effects therefore remain unsupported by robust clinical data.
No. It is an investigational compound without approved therapeutic indications. It is sold for research purposes only in many jurisdictions.