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Background And Development — Practical Notes

By Editorial Desk · published 2025-08-01 · last reviewed 2025-08-28 · Blog

A practical reference on ACTH(4–10): what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.

This page was last updated on 2025-08-28 and is reviewed periodically as new material appears.

Background and Development

Russian regulatory authorities approved the peptide for nasal administration, and it remains listed in the national pharmacopoeia under several trade names. Documented indications include acute ischemic stroke, transient ischemic attacks, traumatic brain injury, and certain ophthalmological and neurological conditions. Physicians also prescribe it for cognitive complaints in older patients, although the evidence base for that use is thinner. Outside Russia and a few neighboring states, the substance is not an approved medicine and is sold instead as a research chemical.

Later generations of the molecule include an N-acetylated form and an amidated form, both marketed online alongside the parent peptide. These variants differ in terminal chemistry and stability, and they are frequently discussed in the same breath even though they have not been compared in controlled trials. Supply outside formal healthcare systems comes largely from laboratories that synthesize peptides to order. Purity and identity of these materials vary widely, and no single body oversees the international trade.

Semax is a synthetic heptapeptide developed in the Soviet Union during the 1980s by researchers at the Institute of Molecular Genetics in Moscow. It was designed as a truncated analog of adrenocorticotropic hormone, retaining only the fragment spanning residues four through ten. Investigators sought a peptide that would preserve the cognitive effects associated with ACTH while eliminating the hormonal stimulation of the adrenal cortex. The compound entered clinical use in Russia during the following decade.

Semax Origin and Molecular Structure

Pharmacological accounts link semax to melanocortin signalling and to modulation of neurotrophic factor expression, particularly brain-derived neurotrophic factor and nerve growth factor. Much of this evidence comes from rodent studies using intranasal delivery, a route chosen because it allows peptides to reach the central nervous system with limited systemic exposure. Whether the same mechanisms operate in humans at comparable magnitude remains an open question. The precise receptor or receptors responsible for the reported behavioural and neuroprotective effects have not been conclusively identified.

Clinical reports describe use in ischaemic stroke, transient ischaemic attack, optic nerve conditions, and cognitive complaints, but most of these studies are small and were conducted in a single region. Systematic reviews have generally described the evidence base as limited in size and variable in methodological quality. Randomised controlled data suitable for international regulatory assessment are scarce. As a result, major treatment guidelines outside Russia do not include the peptide, and interest in it remains largely research-driven rather than routine clinical.

Semax at a glance

PropertyValueNotes
Molecular classSynthetic heptapeptideAnalog of an ACTH fragment
Amino acid lengthSeven residuesMet-Glu-His-Phe-Pro-Gly-Pro
OriginMoscow, 1980sInstitute of Molecular Genetics
Approved regionsRussia and some neighboring statesNot cleared in Western markets
Common trade namesMultiple national brandsSold as a nasal formulation

Semax 的分子背景与结构

Semax 是一种人工合成的七肽,氨基酸序列为 Met-Glu-His-Phe-Pro-Gly-Pro,单字母缩写记作 MEHFPGP。它被归类为促肾上腺皮质激素片段 ACTH(4-10) 的结构类似物,但并不天然存在于生物体内。母体片段 ACTH(4-10) 的序列为 Met-Glu-His-Phe-Arg-Trp-Gly,Semax 替换了中间两个残基,并在羧基端延长了 Pro-Gly-Pro 三肽。这种延长被普遍认为能提升分子对肽酶的耐受性。

该化合物于二十世纪八十年代在俄罗斯被开发,相关工作由俄罗斯科学院分子遗传学研究所的研究团队主导。开发目标并非复制 ACTH 的完整激素活性,而是寻找保留其神经作用方向、同时去除促肾上腺皮质激素释放效应的短肽片段。研究记录显示,这一方向促成了多个相关短肽的合成与筛选,而 Semax 是其中被研究最广泛的一个。当地文献常以 Семакс 这一名称指代它。

研究兴趣主要集中在神经营养因子相关的路径上,包括脑源性神经营养因子与神经生长因子的表达变化。部分实验报告称在特定条件下观察到这些因子的水平上升,但具体信号通路和剂量依赖关系仍未完全厘清。多数公开数据来自细胞模型和动物实验,人体对照研究数量有限。因此,该化合物的作用机制在文献中属于活跃讨论,而非已经确立的定论。

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研发背景与监管地位

当时的短肽研究普遍关注能否穿越血脑屏障、在低剂量下产生中枢效应,Semax 属于这一路线。鼻内给药是其主要使用方式,俄语文献报道的适应症涵盖缺血性卒中、短暂性脑缺血发作、认知功能减退以及视神经病变。这些研究大多发表在当地期刊上,样本规模与终点设置同西方试验惯例存在差异,国际同行对其临床证据的强度看法不一。

各国监管态度分化明显。俄罗斯按处方药管理,部分东欧国家留有使用记录;欧盟与美国未批准其作为药物上市,市面流通品通常标注为研究用化学品。身份差异意味着标示含量、纯度与无菌性缺少统一核查。体育领域还牵涉反兴奋剂名录,跨境携带则受目的地药品法规约束。

Background from the literature

In 1968, they produced the first amino acid analyzer in the world, the JLC-5AH. The company also continued to develop its line of electron microscopes. The JEM-7, in 1964, was the first electronic microscope to include a mechanism for the electrical adjustment of the lens axis. The JEM-100B incorporated an electromagnetic deflection unit as well as an electromagnetic stigmator. The first photomicrograph of atomic arrangement in the world was taken by a JEOL electron microscope, in 1976. Kazuo Ito has expressed the company's philosophy as follows:

The antiandrogenic activity of CPA is dose-dependent. Although CPA is a potent antiandrogen, relatively high doses of CPA are nonetheless required for clinically important AR antagonism. The clinical antiandrogenic efficacy of birth control pills containing CPA, which have only low doses of CPA in them (2 mg/day), often can't be distinguished from that of birth control pills containing other progestins. It is likely that the antiandrogenic effects of CPA-containing birth control pills are due mostly to the ethinylestradiol component and/or suppression of androgen levels, rather than the antiandrogenic activity of the small doses of CPA present in them. CPA has been found to decrease inflammatory acne lesions in males by about 15% at 5 mg/day, by 45% at 25 mg/day, and by 73% at 100 mg/day. A dosage of 100 mg/day CPA can achieve a 65 to 70% reduction in sebum excretion rate in males within 4 weeks of treatment, but doses of 10 mg/day CPA or less are said to have a negligible effect. On the basis of these findings, it has estimated that the threshold dosage of CPA to reduce sebum production may be 5 mg/day in males. In other studies, 25 mg/day CPA resulted in substantial improvement or complete clearance of severe acne in almost all males, whereas 12.5 mg/day was ineffective. CPA has been found to be strongly catabolic in young healthy males. It was shown to result in a mean negative nitrogen balance of 1.2 g at 50 mg/day, 1.4 g at 100 mg/day, and 2.5 g at 200 mg/day. This corresponded to mean losses of lean tissue of 780, 945, and 1,515 g, respectively.

== Medical uses == Setmelanotide is indicated for chronic weight management (weight loss and weight maintenance for at least one year) in people six years and older with obesity due to three rare genetic conditions: pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, and leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes considered pathogenic (causing disease), likely pathogenic, or of uncertain significance. Setmelanotide is the first FDA-approved treatment for these genetic conditions. Setmelanotide is not approved for obesity due to suspected POMC, PCSK1, or LEPR deficiency with variants classified as benign (not causing disease) or likely benign or other types of obesity, including obesity associated with other genetic syndromes and general (polygenic) obesity.

Sources: en.wikipedia.org

Reference notes

== Areas of application == Small molecules are essential components found throughout nature, playing a significant role in various fields such as drug discovery, diagnostics, food science, environmental monitoring, forensics and more. Effectively addressing many global challenges hinges on the comprehensive identification of small molecules in complex samples. These complex mixtures contain thousands of different molecules measurable in a single mass spectrometry run. The identification of unknown small molecules is considered a critical bottleneck in metabolomics, natural product research, and related fields, given that widely over 90% of all small molecules remain unknown. Commonly, analyses were based on targeted approaches that are limited to the rediscovery of known molecules. In contrast, untargeted analysis is a top-down strategy that avoids the need for a prior specific hypothesis on expected small molecules. The focus shifts from asking, "Is molecule X present in the sample?" to "Which (unknown) molecules are present in the sample and might be relevant for downstream analysis?" SIRIUS is designed for the untargeted structural elucidation of unknown molecules, addressing various challenges:

The trial followed participants for 29 days and included 1,033 participants with moderate or severe COVID-19; 515 participants received baricitinib plus remdesivir, and 518 participants received placebo plus remdesivir. Recovery was defined as either being discharged from the hospital or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. The median time to recovery from COVID-19 was seven days for baricitinib plus remdesivir and eight days for placebo plus remdesivir. The odds of a patient's condition progressing to death or being ventilated at day 29 was 31% lower in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. The odds of clinical improvement at day 15 was 30% higher in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. For all of these endpoints, the effects were statistically significant. The EUA was issued to Eli Lilly and Company. In November 2020, the World Health Organization (WHO) updated its guideline on therapeutics for COVID-19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO Solidarity trial. In November 2020, the FDA issued an emergency use authorization (EUA) for the combination of baricitinib with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized people aged two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

=== May === 1 May – Former US President Donald Trump arrives in Aberdeen to visit his Scottish golf properties. 2 May – The Scottish Government reverses plans to give £46m to colleges and universities, having identified the money as an "essential saving". 3 May – The SNP signs a contract with a new auditor, Manchester-based AMS Accountants Group. 4 May – Deputy First Minister Shona Robison confirms the Scottish Government will go ahead with its pledge to provide free school meals for all primary school pupils in Scotland. 5 May – Junior doctors in Scotland vote to stage a three-day strike over their demand for a 23.5% above inflation pay increase from the Scottish Government. 10 May – UK Prime Minister Rishi Sunak urges the Scottish Government to re-think its plans to introduce Highly Protected Marine Areas in Scottish waters, which would restrict fishing and other human activities to preserve the environment. 12 May – The Stand Comedy Club reinstates an Edinburgh Fringe show to be staged by SNP MP Joanna Cherry after previously cancelling it after it said staff were uncomfortable with her views about transgender people. 15 May – Stagecoach Group launches a driverless bus service on the Forth Road Bridge, believed to be the world's first. 16 May – COVID-19 in Scotland: The rules requiring people to wear face masks in Scottish care homes and healthcare settings come to an end after three years. 17 May First Minister Humza Yousaf attends his first audience with King Charles III at Buckingham Palace.

Sources: en.wikipedia.org

Notes from published material

== Function == Microproteins function as post-translational regulators. Microproteins disrupt the formation of heterodimeric, homodimeric, or multimeric complexes. Furthermore, microproteins can interact with any protein that requires functional dimers to function normally. The primary targets are transcription factors that bind to DNA as dimers. Microproteins regulate these complexes by creating homotypic dimers with the targets and inhibit protein complex function. The two types of miP inhibitions are: homotypic miP inhibition and heterotypic miP inhibition. In homotypic miP inhibition, microproteins interact with proteins with similar protein-protein interaction (PPI) domain. In heterotypic miP inhibition, microproteins interact with proteins with different but compatible PPI domain. In both types of inhibition, microproteins interfere and prevent the PPI domains from interacting with their normal proteins. Microproteins plays roles in biological process such as immunity and inflammation, cancer and cell cycle regulation, cellular transport, muscle and heart functions, gene expression and genome maintenance, proteostasis, and metabolic homeostasis.

== Interactions == There are a few types of medications that interact with valsartan. Combined use with nonsteroidal anti-inflammatory drugs (NSAID) such as naproxen or ibuprofen can result in kidney injury in people who are elderly, dehydrated, or have reduced kidney function. One study conducted Lapi F., et al. found that there was no increased risk of kidney injury when only using either a diuretic or angiotensin receptor blocker with an NSAID but did find an increased risk when all three medications were used together. Valsartan usage with angiotensin receptor blocker, ACE inhibitors, or aliskiren results in additive side effects.

=== February === 2 February – The President of the European Parliament Roberta Metsola began a two-day visit to Ireland. She addressed both Houses of the Oireachtas as part of the 50th anniversary (1 January 1973) of Ireland joining the European Economic Community (now the European Union), and met the president, taoiseach, and tánaiste. 6 February – The Lia Fáil – the coronation stone for the High Kings of Ireland on the Hill of Tara – was vandalised when the word "Fake" was spray painted on the 5,000-year-old granite stone. 7 February Government ministers met with aviation and police authorities for briefing on illegal drone activity at Dublin Airport between 4–6 February which forced suspension of flying and diversions of flights to other airports. Munster Technological University announced that it was investigating a significant breach of its information technology and telephone systems. It was later confirmed that the university suffered a ransomware cyber attack. 9 February An Coimisiún Toghcháin (the Irish electoral commission) was established under the Electoral Reform Act 2022 to oversee elections in Ireland. Microsoft announced that it would cut 120 jobs from its Irish-based workforce as part of a global cost-cutting plan. 12 February – Munster Technological University announced that information stolen from its computer systems in a cyber attack a week ago had appeared on the dark web. 18 February – Up to 50,000 people participated in an "Ireland for All" march and rally in Dublin in support of refugees and asylum seekers, and opposing racism and far-right groups.

=== Protein labeling === Protein labeling use a short tag to minimize disruption of protein folding and function. Transition metals are used to link specific residues in the tags to site-specific targets such as the N-termini, C-termini, or internal sites within the protein. Examples of tags used for protein labeling include biarsenical tags, Histidine tags, and FLAG tags.

Sources: en.wikipedia.org

Frequently asked questions

Where was Semax developed?

It originated at the Institute of Molecular Genetics in Moscow during the 1980s. The work was carried out by a Russian research group that specialized in peptide neuropharmacology.

Is Semax an approved medication anywhere?

It is registered as a medicine in Russia and has been used clinically there for decades. No regulatory agency in Western Europe or North America has approved it for any indication.

What is the relationship to ACTH?

Semax corresponds to the four-to-ten fragment of adrenocorticotropic hormone. Because it omits the first three residues, it lacks the adrenal-stimulating action of the full hormone.

What is semax derived from?

It is described as a synthetic analogue of the ACTH(4–10) fragment, a short segment of adrenocorticotropic hormone. Its sequence differs from that fragment and includes two proline residues, which influence stability and behaviour in solution.

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