Everything below concerns ACTH fragment. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-10-10. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
Development of the compound took place in the Soviet Union during the 1980s, largely through peptide research groups affiliated with the Shemyakin-Ovchinnikov Institute and Moscow State University. Investigators screened fragments of adrenocorticotropic hormone for activity on the central nervous system while attempting to separate cognitive effects from hormonal ones. The shortened sequence was selected because it retained behavioral activity in animal models without stimulating corticosteroid release. Early publications described the molecule as an ACTH(4-10) analog.
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.
The compound was developed during the 1980s at the Institute of Molecular Genetics in Moscow as part of research on fragments of adrenocorticotropic hormone. Early work examined short ACTH-derived sequences that retained neurotrophic effects while lacking the endocrine activity of the full hormone. Semax entered clinical use in Russia during the 1990s, where it received registration for several neurological indications. Outside that region it remained primarily a laboratory research material rather than an approved therapeutic. English-language literature on it grew more slowly and frequently cited the original Russian studies.
Terminology around the compound varies by source. It appears in catalogues and papers as Semax, as the heptapeptide ACTH(4-7)-Pro-Gly-Pro, and under various alphanumeric laboratory codes used by individual suppliers. These names refer to the same sequence but may imply different salt forms, purity grades, or counter-ions. Peptide databases usually list the free base mass, while product descriptions sometimes report acetate or trifluoroacetate salts with a different formula weight. Because naming conventions for research peptides are not standardised across vendors, checking the declared sequence and measured mass is more reliable than relying on a trade name alone.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C37H51N9O10S | Seven-residue peptide |
| Molecular mass | 813.9 Da | Monoisotopic value |
| Appearance | White to off-white powder | Lyophilized form |
| Solubility | Freely soluble in water | Also soluble in saline and polar solvents |
| Storage (dry) | -20 °C or lower | Desiccated, protected from light |
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.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Its chain combines the first seven residues of corticotropin with a C-terminal proline-glycine-proline extension, a modification intended to slow enzymatic breakdown. The free peptide has a molecular mass near 813.9 daltons. It belongs to the class of ACTH-derived fragments studied for central nervous system activity rather than for adrenal steroid stimulation. This structural relationship to a natural hormone fragment is the usual starting point for describing the compound in the literature.
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.
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.
== Toxicity == Studies carried out on the toxicity of convulxin show that symptoms are a function of the dose. The effects of the toxin stand out through the sudden and brief duration of the symptoms after exposure. In mice, low doses (5 μg/animal) administered intravenously (I.V) elicited tachypnea, followed by apnea, within 20 seconds. The ED50 for brief duration apnea was determined to be 180 μg/kg. Higher doses (10 μg/animal) evoked intense convulsive crisis, and usually ended with the death of the animal. LD50 was determined to be 524 μg/kg. Intraperitoneal (I.P.) administration of up to 200 μg/animal proved to be ineffective. In cats, I.V. injections of 100 μg/kg showed respiratory disturbances, miosis, salivation, abdominal cramps, nystagmus, loss of equilibrium, convulsions and sometimes a brief phase of hypotonia. The ED50 dose for convulsions is 80 μg/kg. The majority of animals recovered within 30 minutes. In dogs, the effect of convulxin showed two stages. After I.V. injection of 100-125 μg/kg they became excited, barked and exhibited loss of equilibrium, respiratory disturbances, nystagmus, urination, defecation and vomiting. After recovery, two out of five animals had intermittent crisis of clonic convulsions that appeared after 24 hours and lasted until their death. The other three dogs showed periods of vivid agitation alternating with torpor. While the lethal dose in humans is not yet known, what has been discovered is that the level of toxic effects depends on the origin of the snake. As for a cure, so far a polyvalent snake antivenom is being used.
== Pharmacokinetic details == More than 90% of verapamil is absorbed when given orally, but due to high first-pass metabolism, bioavailability is much lower (10–35%). It is 90% bound to plasma proteins and has a volume of distribution of 3–5 L/kg. It takes 1 to 2 hours to reach peak plasma concentration after oral administration. It is metabolized in the liver to at least 12 inactive metabolites (though one metabolite, norverapamil, retains 20% of the vasodilatory activity of the parent drug). As its metabolites, 70% is excreted in the urine and 16% in feces; 3–4% is excreted unchanged in urine. This is a nonlinear dependence between plasma concentration and dosage. Onset of action is 1 to 2 hours after oral dosage, and 3 to 5 minutes after intravenous bolus dosage. Biphasic or triphasic following IV administration; terminal elimination half-life is 2–8 hours. Plasma half-life of 2–8 or 4.5–12 hours after single oral dose or multiple oral doses, respectively. It is not cleared by hemodialysis. It is excreted in human milk. Because of the potential for adverse reaction in nursing infants, nursing should be discontinued while verapamil is administered.
=== Neuronal Control === The most well studied is through the action of extra-pancreatic glucose sensors, including neurons found in the brain, which exert control over the alpha cells in the pancreas. The pancreas is controlled by both the sympathetic nervous system and the parasympathetic nervous system, although the method these two systems use to control the pancreas appears to be different. Sympathetic control of the pancreas appears to originate from the sympathetic preganglionic fibers in the lower thoracic and lumbar spinal cord. According to Travagli et al. "axons from these neurons exit the spinal cord through the ventral roots and supply either the paravertebral ganglia of the sympathetic chain via communicating rami of the thoracic and lumbar nerves, or the celiac and mesenteric ganglia via the splanchnic nerves. The catecholaminergic neurons of these ganglia innervate the intrapancreatic ganglia, islets and blood vessels..." The exact nature of the effect of sympathetic activation on the pancreas has been difficult to discern. However, a few things are known. It appears that stimulation of the splanchnic nerve lowers plasma insulin levels possibly through the action of α2 adrenoreceptors on beta cells. It has also been shown that stimulation of the splanchnic nerve increases glucagon secretion. Both of these findings together suggest that sympathetic stimulation of the pancreas is meant to maintain blood glucose levels during heightened arousal. Parasympathetic control of the pancreas appears to originate from the Vagus nerve.
== Significance == The transmembrane region of many integral membrane proteins consists of one or more alpha helices. The orientations and interactions of these helices directly affect cell signaling and molecular transport across the bilayer. The hydrophobic environment of the phospholipid tails in turn modulates the position and structure of such domains and thus may influence protein function. Conversely, the bilayer itself can (locally) change the thickness of its hydrocarbon region to interact optimally with hydrophobic regions of a transmembrane protein (a.k.a. hydrophobic matching). WALPs provide an effective model for studying such interactions because of their systematic design of a core of hydrophobic, alternating alanine and leucine regions. This core is readily manipulated by extending or decreasing the number of amino acids. Another key feature is the presence of "anchoring" residues at the ends of the helix, which are tryptophan residues in the WALP versions. Substituting the anchoring tryptophan residues for charged residues, such as lysine, yields "KALP" peptides. This class of model peptides has proved useful for studying the impact of changes in lipid composition on peptide insertion. Following detailed experimental studies by various techniques, the WALP and related peptides have become commonly used model systems in computational biology.
Sources: en.wikipedia.org
==== Vaso-occlusive crisis ==== Also termed "sickle cell crisis" or "sickling crisis", the vaso-occlusive crisis (VOC) manifests principally as extreme pain, most often affecting the chest, back, legs, and/or arms. The underlying cause is sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Milder crises can be managed with nonsteroidal anti-inflammatory drugs. For more severe crises, patients may require inpatient management for intravenous opioids. Vaso-occlusive crisis involving organs such as the lungs or the penis are considered an emergency and treated with red blood cell transfusions. A VOC can be triggered by anything which causes blood vessels to constrict; this includes physical or mental stress, cold, and dehydration. "After Haemoglobin S (HbS) deoxygenates in the capillaries, it takes some time (seconds) for HbS polymerization and the subsequent flexible-to-rigid transformation. If the transit time of RBC through the microvasculature is longer than the polymerization time, sickled RBC will lodge in the microvasculature."
Some paleolithic hunter-gatherers consumed a significant amount of meat and possibly obtained most of their food from hunting, while others were believed to have a primarily plant-based diet. Most, if not all, are believed to have been opportunistic omnivores. One hypothesis is that carbohydrate tubers (plant underground storage organs) may have been eaten in high amounts by pre-agricultural humans. It is thought that the Paleolithic diet included as much as 1.65–1.9 kg (3.6–4.2 lb) per day of fruit and vegetables. The relative proportions of plant and animal foods in the diets of Paleolithic people often varied between regions, with more meat being necessary in colder regions (which were not populated by anatomically modern humans until c. 30,000 – c. 50,000 BP). It is generally agreed that many modern hunting and fishing tools, such as fish hooks, nets, bows, and poisons, were not introduced until the Upper Paleolithic and possibly even Neolithic. The only hunting tools widely available to humans during any significant part of the Paleolithic were hand-held spears and harpoons. There is evidence of Paleolithic people killing and eating seals and elands as far as c. 100,000 BP. On the other hand, buffalo bones found in African caves from the same period are typically of very young or very old individuals, and there is no evidence that pigs, elephants, or rhinos were hunted by humans at the time. Paleolithic peoples suffered less famine and malnutrition than the Neolithic farming tribes that followed them.
=== Refresh frequency limits for HDR video === Color depth of 10 bpc (30 bit/px or 1.07 billion colors) is assumed for all formats in these tables. This color depth is a requirement for various common HDR standards, such as HDR10. It requires 25% more bandwidth than standard 8 bpc video. HDR extensions were defined in version 1.4 of the DisplayPort standard. Some displays support these HDR extensions, but may only implement HBR2 transmission mode if the extra bandwidth of HBR3 is unnecessary (for example, on 4K 60 Hz HDR displays). Since there is no definition of what constitutes a "DisplayPort 1.4" device, some manufacturers may choose to label these as "DP 1.2" devices despite their support for DP 1.4 HDR extensions. As a result, DisplayPort "version numbers" should not be used as an indicator of HDR support.
The interference with mRNA proofreading has been exploited to treat genetic diseases that result from premature stop codons (leading to early termination of protein synthesis and truncated proteins). Aminoglycosides can cause the cell to overcome the stop codons, insert a random amino acid, and express a full-length protein. Gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory to induce them to grow full-length proteins. CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In approximately 10% of CF cases, the mutation in this gene causes its early termination during translation, leading to the formation of a truncated and non-functional CFTR protein. It is believed that gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination codon, causing the ribosome to "skip" over the stop sequence and to continue with the normal elongation and production of the CFTR protein. In a short randomized controlled trial, CF patients receiving gentamicin showed better electrophysiological parameters after treatment.
The protective effect of breastfeeding against obesity is consistent, though small, across many studies. A 2013 longitudinal study reported less obesity at ages two and four years among infants who were breastfed for at least four months.
Sources: en.wikipedia.org
In January 1996, Wenger guided the club to their first piece of silverware as Nagoya defeated Sanfrecce Hiroshima to win the Emperor's Cup. Two months later they triumphed in the Super Cup, beating Yokohama Marinos 2–0. The success bolstered Nagoya's status in Japanese football, as well as Wenger's reputation; he was somewhat startled by the praise and idolisation that came his way. Midway through the 1996 league season, Wenger's former club Strasbourg enquired about the possibility of him returning to manage them. He turned down the offer, as he had been approached by Arsenal. David Dein had remained in contact with Wenger after their first meeting, and frequently sent him video tapes of matches to garner his opinions; "He was my personal pundit," the vice-chairman recalled. The Arsenal board rebuffed Dein's suggestion to appoint Wenger as early as 1995, but concerns over George Graham's successor Bruce Rioch meant they were more open-minded about hiring him since his stint in Japan. Wenger managed Nagoya for the final time on 28 August 1996 and delivered a farewell speech, thanking the fans in Japanese. Assessing his time in Japan, biographer Jasper Rees felt Wenger had left a mixed legacy at the club, as the immediate success was followed by fluctuating league finishes; it was not until 2010 that Nagoya (under Stojković) won their first title.
== History == The earliest human activity in Ningxia can be traced back to 30,000 years ago, with remains of the Shuidonggou culture found in Lingwu. As a frontier zone between nomadic pastoralists and sedentary farmers, Ningxia was a frequent seat of war and incursions by non-Chinese tribes. Ningxia and its surrounding areas were incorporated into the Qin as the Beidi Commandery as early as the 3rd century BC. To pacify the region, the imperial government established military colonies to reclaim land. In addition, horse pasturages were founded under the Imperial Stud to safeguard the supply of army horses, as early as the Western Han dynasty (206 BC – AD 9). Throughout the Han dynasty and the Tang dynasty there were several large cities established in the region. The Liang Province rebellion at the end of the Han dynasty affected Ningxia. By the 11th century the Tangut people had established the Western Xia dynasty on the outskirts of the then-Song dynasty. Jews also lived in Ningxia, as evidenced by the fact that in 1489, after a major flood destroyed Torah scrolls in Kaifeng, a replacement set was sent to the Kaifeng Jews by the Ningbo and Ningxia Jewish communities. It then came under Mongol domination after Genghis Khan conquered Yinchuan in the early 13th century. Muslims from Central Asia also began moving into Ningxia from the west. By the late 17th century, Ningxia had become a weaving centre, producing many early Chinese carpets. The Muslim Dungan Revolt of the 19th century affected Ningxia. In 1914, Ningxia was merged with the province of Gansu.
== Residual topology == Residual topology is a descriptive stereochemical term to classify a number of intertwined and interlocked molecules, which cannot be disentangled in an experiment without breaking of covalent bonds, while the strict rules of mathematical topology allow such a disentanglement. Examples of such molecules are rotaxanes, catenanes with covalently linked rings (so-called pretzelanes), and open knots (pseudoknots) which are abundant in proteins. The term "residual topology" was suggested on account of a striking similarity of these compounds to the well-established topologically nontrivial species, such as catenanes and knotanes (molecular knots). The idea of residual topological isomerism introduces a handy scheme of modifying the molecular graphs and generalizes former efforts of systemization of mechanically bound and bridged molecules.
== Veterinary use == The medication is approved in the United States for the treatment of atopic dermatitis in dogs and cats. Unlike the human form of the medication, the lower doses used in pets mean the drug acts as an immunomodulator and has fewer side effects than in humans. The benefits of using this product include the reduced need for concurrent therapies to bring the condition under control. It is available as an ophthalmic ointment for dogs called Optimmune, manufactured by Intervet, which is part of Merck. It is also available for dogs and cats via an oral solution called Atopica, manufactured by Elanco. It is also used to treat sebaceous adenitis (immune response against the sebaceous glands), pemphigus foliaceus (autoimmune blistering skin disease), Inflammatory bowel disease, perianal fistulas (anal inflammatory disease), and myasthenia gravis (a neuromuscular disease).
Sources: en.wikipedia.org
It is a synthetic peptide of seven amino acids. Its backbone corresponds to a fragment of adrenocorticotropic hormone extended at the carboxyl end. The material is distributed as a lyophilized solid for laboratory use.
The extension was introduced to slow enzymatic breakdown of the peptide in biological systems. Natural ACTH fragments are degraded rapidly by peptidases. Adding the tripeptide was intended to extend the window during which the molecule remains intact.
Most published work consists of animal experiments conducted in a small number of laboratories. Human data are limited in number and size. Whether the observed effects translate into reliable clinical benefit is still unresolved.
It is a synthetic seven-amino-acid peptide built from the ACTH(4-7) sequence plus a Pro-Gly-Pro tail. It belongs to the family of short ACTH fragments studied for nervous-system effects. Its backbone contains only standard amino acids.