A practical reference on ACTH fragment: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-08-01. Anything still debated is marked as such rather than presented as settled.
Development took place during the 1980s at institutes of the Russian Academy of Sciences, where peptide fragments of ACTH were screened for cognitive and neuroprotective effects. The compound received regulatory approval in Russia as a nasal preparation, marketed for conditions such as ischemic stroke, transient ischemic attacks, and optic nerve disorders. Registration in other countries has not followed. Most published clinical reports originate from a small number of Russian research groups, and independent replication outside that setting remains limited. The regulatory status therefore differs sharply between Russia and the rest of the world.
Laboratory work points toward modulation of neurotrophic signaling, particularly expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal tissue. Studies also describe effects on monoamine turnover, inflammatory mediators, and oxidative markers. These observations come mainly from animal models and cultured cells, so the causal chain in humans is not firmly established. Whether the reported molecular changes translate into measurable clinical benefit is an open question. Reviews generally present the mechanism as plausible rather than demonstrated.
Clinical evidence consists largely of small trials with modest sample sizes, often without independent replication. Reported endpoints include cognitive scores, recovery after stroke, and visual function, but study designs vary widely and few trials meet contemporary reporting standards. Systematic reviewers have noted a high risk of bias in several of these reports. No large multicenter trial conducted outside Russia has been published. The compound is therefore best described as investigational in most jurisdictions, with its clinical role still unresolved.
溶液状态的稳定性明显低于冻干粉。肽类在水溶液中可能经历水解、氧化与聚集，其中甲硫氨酸和天冬酰胺等残基常是敏感位点。Semax 含有甲硫氨酸，因此氧化风险相对突出。工作液一般主张现配现用，或冷藏并在数日内用尽。缓冲液种类、pH 和离子强度都会影响降解速率，而关于最佳条件的公开数据并不统一。
常规纯度与身份确认依赖反相高效液相色谱，并辅以质谱测定分子量。氨基酸组成分析可用于验证序列构成，肽图分析则能进一步定位修饰或降解产物。杂质谱通常关注缺失序列肽、截短片段和氧化产物。不同方法的检出限并不相同，因此各实验室报告的纯度数值不宜直接横向比较。
| Property | Value | Notes |
|---|---|---|
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | Heptapeptide; ACTH(4-10) analog extended at C-terminus |
| Molecular mass | ~813.9 Da | Free peptide, unmodified |
| Appearance | White to off-white powder | Typical lyophilized solid |
| Solubility | Soluble in water and saline | Also soluble in common aqueous buffers |
| Storage (solid) | -20 °C, desiccated | Protect from moisture and repeated thawing |
The compound is registered in Russia as a pharmaceutical product, most commonly formulated as a nasal solution, and has been used in that setting since the 1990s. Outside that jurisdiction it is generally handled as a research chemical rather than an approved medicine. Regulatory status therefore differs sharply between countries, and material sold internationally may not correspond to the Russian pharmaceutical formulation. Documentation with commercial samples is typically limited to a certificate of analysis covering purity and identity, not clinical status or local legal classification.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It corresponds to the ACTH(4-7) fragment extended at the C-terminus by a Pro-Gly-Pro tripeptide, an addition intended to slow enzymatic breakdown. The molecular formula is C37H51N9O10S and the molecular mass is approximately 814 daltons. In the literature it is often described as an ACTH(4-10) analog, although that label reflects a naming convention as much as a precise structural relationship. The compound was developed in Russia and remains most closely associated with that research tradition.
Laboratory descriptions of the material are consistent across suppliers. It appears as a white to off-white lyophilized powder that dissolves readily in water and in polar organic solvents such as dimethyl sulfoxide. Aqueous solutions are clear and colorless at low concentrations. Because the peptide contains methionine, oxidation at the sulfur atom is a recognized degradation pathway, and handling notes usually call for protected, desiccated storage. Reported purity for research-grade lots is generally above 95 percent as measured by reversed-phase high-performance liquid chromatography.
稳定性主要由水解与氧化两条路径支配。肽键在中性或弱酸性条件下相对稳定，遇到强碱或长时间高温则明显断裂；甲硫氨酸侧链容易被氧化成亚砜，使主峰前移并拉低实际含量。金属离子、光照和反复冻融会进一步促进降解或聚集。冻干粉在低温避光条件下可存放较长时间，配制后的水溶液通常需要冷藏并尽快用完。
纯度评估以反相高效液相色谱为主，通过主峰面积百分比给出粗略结果，再配合电喷雾质谱核对分子量。氨基酸分析可验证组成比例，手性色谱或毛细管电泳用于检查残基构型。常见杂质包括缺失序列的短肽、氧化产物与二聚体。由于多数市售品不附带完整检验报告，独立第三方检测常被用来核实标称值。
Published research on this peptide originates mainly from Russian laboratories, and the wider international literature is comparatively thin. Studies have used rodent models of stroke, hypoxia, and memory tasks, with a smaller number of human trials reported. Reported outcomes include changes in attention and memory measures, along with effects on neurotrophic factor expression in some experiments. Small sample sizes, inconsistent dosing protocols, and limited independent replication are widely noted limitations, so the strength of the clinical evidence remains an open question.
Semax is a synthetic heptapeptide whose sequence is Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues correspond to the ACTH(4-10) fragment, while the terminal Pro-Gly-Pro extension was added to improve metabolic stability. Its molecular formula is C37H51N9O10S and its monoisotopic mass is approximately 813.9 Da. The compound is classified as a peptide research chemical and as a registered pharmaceutical product in Russia, but it does not hold marketing approval in the European Union or the United States. Naming conventions vary across supplier catalogs.
=== Signalling === Once cleaved, PAR1 can activate G-proteins that bind to several locations on its intracellular loops. For example, PAR1 in conjunction with PAR4 can couple to and activate G-protein G12/13 which in turn activates Rho and Rho kinase. This pathway leads to the quick alteration of platelet shape due to actin contractions that lead to platelet mobility, as well as the release of granules which are both necessary for platelet aggregation. Coupling can also occur with Gq, leading to phospholipase C-β activation; this pathway results in the stimulation of protein kinase C (PKC) which impacts platelet activation. Additionally, both PAR1 and PAR4 can couple to G-protein q which stimulates intracellular movement for Calcium ions that serve as second messengers for platelet activation. This also activates protein kinase C which stimulates platelet aggregation and therefore blood coagulation further down the pathway.
=== 1.2a === DisplayPort version 1.2a was released in January 2013 and may optionally include VESA's Adaptive Sync. AMD's FreeSync uses the DisplayPort Adaptive-Sync feature for operation. FreeSync was first demonstrated at CES 2014 on a Toshiba Satellite laptop by making use of the Panel-Self-Refresh (PSR) feature from the Embedded DisplayPort standard, and after a proposal from AMD, VESA later adapted the Panel-Self-Refresh feature for use in standalone displays and added it as an optional feature of the main DisplayPort standard under the name "Adaptive-Sync" in version 1.2a. As it is an optional feature, support for Adaptive-Sync is not required for a display to be DisplayPort 1.2a-compliant.
== Climate == The climate of Stanley is classified as a subpolar oceanic climate (Köppen Cfc), bordering very closely on a polar climate (ET). Nowadays it barely avoids classification as ET because the mean temperature is greater than 10 °C (50 °F) for two months of the year. Unlike typical tundra climates, however, the winters are very mild, and vegetation grows there that normally could not in a climate this close to a polar climate. Contrast this with Churchill, Manitoba, which also has a near-tundra climate but is much more continental in nature. The Falkland Islands have displayed a warming trend in recent years; the mean daily January maximum for Mount Pleasant for the years 1999-2012 is 15.1 °C (59.2 °F) compared to Stanley's 1961-90 average of 14.1 °C (57.4 °F). Formerly, Stanley had a tundra climate (ET), due to cool summer temperatures (the mean temperature was less than 10 °C or 50 °F in the hottest month). Like the rest of the archipelago, Stanley has more or less even temperatures through the year and strong westerlies. Precipitation, averaging 544 mm (21.42 in) a year, is nonetheless relatively low, and evenly spread throughout the year. Typically, at least 1 mm (0.039 in) of rain will be recorded on 125.2 days of the year. The islands receive 36.3% of possible sunshine, or around 1500–1600 hours a year, a level similar to southern parts of England. Daytime temperatures are similar to the Northern Isles of Scotland, though nights tend to be somewhat colder, with frost occurring on more than 1 in 3 nights (128.4 nights). Snow occurs in the winter.
=== P granules === Another example of liquid droplets in cells are the germline P granules in Caenorhabditis elegans. These granules separate out from the cytoplasm and form droplets, as oil does from water. Both the granules and the surrounding cytoplasm are liquid in the sense that they flow in response to forces, and two of the granules can coalesce when they come in contact. When (some of) the molecules in the granules are studied (via fluorescence recovery after photobleaching), they are found to rapidly turnover in the droplets, meaning that molecules diffuse into and out of the granules, just as expected in a liquid droplet. The droplets can also grow to be many molecules across (micrometres) Studies of droplets of the Caenorhabditis elegans protein LAF-1 in vitro also show liquid-like behaviour, with an apparent viscosity
Sources: en.wikipedia.org
== Synthesis == Neuropeptides are synthesized from inactive precursor proteins called prepropeptides. Prepropeptides contain sequences for a family of distinct peptides and often contain duplicated copies of the same peptides, depending on the organism. In addition to the precursor peptide sequences, prepropeptides also contain a signal peptide, spacer peptides, and cleavage sites. The signal peptide sequence guides the protein to the secretory pathway, starting at the endoplasmic reticulum. The signal peptide sequence is removed in the endoplasmic reticulum, yielding a propeptide. The propeptide travels to the Golgi apparatus where it is proteolytically cleaved and processed into multiple peptides. Peptides are packaged into dense core vesicles, where further cleaving and processing, such as C-terminal amidation, can occur. Dense core vesicles are transported throughout the neuron and can release peptides at the synaptic cleft, cell body, and along the axon. A single animal may use hundreds of different neuropeptides. In C. elegans, for example, 120 genes specify more than 250 neuropeptides.
==== Evolution of animal synthesis ==== Ascorbic acid is a common enzymatic cofactor in mammals used in the synthesis of collagen, as well as a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize this molecule has not always been conserved. In fact, anthropoid primates, Cavia porcellus (guinea pigs), teleost fishes, most bats, and some passerine birds have all independently lost the ability to internally synthesize vitamin C in either the kidney or the liver. In all of the cases where genomic analysis was done on an ascorbic acid auxotroph, the origin of the change was found to be a result of loss-of-function mutations in the gene that encodes L-gulono-γ-lactone oxidase, the enzyme that catalyzes the last step of the ascorbic acid pathway outlined above. One explanation for the repeated loss of the ability to synthesize vitamin C is that it was the result of genetic drift; assuming that the diet was rich in vitamin C, natural selection would not act to preserve it.
Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, which in turn results in buildup of acetaldehyde, a toxic metabolite of ethanol with unpleasant effects. The medication or drug is commonly used to treat alcohol use disorder, and results in immediate hangover-like symptoms upon consumption of alcohol, this effect is widely known as disulfiram effect.
== Mechanism == As a derivative of EDTA, dexrazoxane chelates iron and thus reduces the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. The exact chelation mechanism is unknown, but it has been postulated that dexrazoxane can be converted into ring-opened form intracellularly and interfere with iron-mediated free radical generation that is in part thought to be responsible for anthracycline induced cardiomyopathy. It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.
Serotonylation has been reported in various cell types and tissues, including both serotonergic and dopaminergic neurons, enterochromaffin cells, cancer-associated fibroblasts, pancreatic 𝛽-cells, CD8+ T cells, pulmonary endothelial cells, platelets, neutrophils, mammary epithelial cells, vascular smooth muscle, and cells of the intestines. Serotonylation is known to influence both tumorigenesis and cancer metastasis, and has been implicated in several types of cancer, including colorectal cancer, neuroendocrine prostate cancer, pancreatic cancer, hepatocellular carcinoma, and ependymomas (brain cancer).
Sources: en.wikipedia.org
Semax is a synthetic seven-amino-acid peptide derived from a fragment of corticotropin. It is used in Russia as a nasal preparation, while elsewhere it is studied as a research compound. It is not approved as a medicine in most countries.
Its sequence corresponds to the 4-10 region of corticotropin extended by three residues. This fragment lacks the region responsible for adrenal steroid release, so it is explored for neural rather than hormonal effects. The relationship explains the compound's classification among ACTH-derived peptides.
It holds approval in Russia for several neurological indications as a nasal spray or drop formulation. Regulatory agencies in the United States and the European Union have not approved it. Products sold elsewhere are generally labeled for research use only.
一般不建议常温长期保存。多数说明指向 -20 °C 冷冻避光。常温运输通常被视为短期可接受，但会加快降解风险。