If you have been reading about bioregulator 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 2026-04-20. Where a claim depends on a specific study, the study is described rather than over-claimed.
The compound is described in the literature as a derivative of epithalamin, a preparation obtained from bovine pineal tissue. Work on this peptide family was carried out mainly by a research group in Saint Petersburg beginning in the 1980s, and the substance was later registered for clinical use in Russia under the name Epitalon. Outside that region it is generally treated as a research chemical rather than an approved medicine. Statements about its biological activity rest on a relatively small number of studies, and independent replication remains limited.
In its supplied form epitalon is a white to off-white powder, usually lyophilized and often hygroscopic. It dissolves readily in water and in aqueous buffers, and it is commonly handled as the acetate or trifluoroacetate salt to improve stability during purification and drying. The amide backbone is labile in aqueous media, so solutions are less durable than the dry solid. Handling notes in the chemical literature therefore emphasize keeping the powder dry, cool and shielded from light until it is dissolved.
Identity and purity are established with reversed-phase high-performance liquid chromatography and mass spectrometry. The chromatogram shows the main peak and any truncated or oxidised by-products, while the mass spectrum confirms the expected 390 dalton mass. Amino acid analysis can corroborate composition when a sample's origin is uncertain. Counterion content, particularly residual trifluoroacetate from purification, is frequently reported alongside purity because it shifts the net mass of the solid.
Reference material is normally supplied as a lyophilised powder in a sealed vial. Product literature typically recommends storage at minus twenty degrees Celsius or colder, protected from light and moisture. Freeze-thaw cycling is usually avoided because repeated condensation can introduce water into the vial. Working solutions are commonly prepared fresh, aliquoted, and kept cold for short periods rather than stored at ambient temperature. Labelling the date of opening helps track how long a vial has been in use.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic tetrapeptide | Four residues, linear chain |
| Residue sequence | Ala-Glu-Asp-Gly | Single-letter form AEDG |
| Calculated mass | 390.3 daltons | Value for the free, uncharged form |
| Appearance | White to off-white powder | Usually supplied lyophilized |
| Solubility | Freely soluble in water | Often handled as a salt form |
Epitalon is a synthetic tetrapeptide with the residue sequence alanine-glutamate-aspartate-glycine, commonly abbreviated AEDG. Its monoisotopic mass is approximately 390.35 daltons, and it is usually supplied as a lyophilised trifluoroacetate or acetate salt. The compound was derived from a pineal gland extract called epithalamin, a heterogeneous preparation investigated in the former Soviet Union. Researchers associated with the Saint Petersburg Institute of Bioregulation and Gerontology described the tetrapeptide as a constituent fragment of that extract. Commercial material is offered as a laboratory reagent rather than as a finished pharmaceutical product.
Literature searches for this compound must account for several spelling variants. Indexing databases contain epitalon, epithalon, epithalone, and AEDG, and relevant records are scattered across Russian-language and English-language journals that do not consistently cross-cite. Early publications describe the parent extract as a mixture of many peptides, whereas later work addresses the single synthetic tetrapeptide. That shift in nomenclature complicates comparison between studies, because extract data and tetrapeptide data are sometimes cited interchangeably. A search strategy omitting the alternate spellings will return an incomplete set of references.
Regulatory treatment differs by country. No formulation of epitalon holds a marketing authorisation as a medicine in the United States or the European Union, where material sold for laboratory use is handled as a research chemical and is not intended for human consumption. In Russia, several short peptide preparations from the same institute's peptide series are registered medicinal products, and epitalon appears in that national context. Elsewhere it is frequently offered as a cosmetic ingredient, a category with lighter requirements. Advertising claims about longevity or disease prevention are restricted in most jurisdictions, which limits how sellers describe the compound.
Freeze-dried epitalon is normally kept at minus twenty degrees Celsius in a sealed, desiccated container, protected from light. Short excursions at ambient temperature during shipping are generally tolerated, but repeated warming and cooling cycles encourage moisture uptake, which shortens shelf life. Once dissolved, the peptide is far less stable than the solid: aqueous solutions are subject to hydrolysis and to deamidation at the aspartate and glutamate residues. Working solutions are therefore held refrigerated and used within days, and repeated freezing and thawing of the same vial is best avoided.
The four residues give epitalon a molecular formula of C14H22N4O9 and a molecular weight near 390.35 daltons. The presence of two acidic residues, glutamate and aspartate, makes the free peptide strongly acidic, while the alanine and glycine ends provide neutral, nonpolar character. This combination produces a molecule with substantial water solubility. Because there are no cysteine, methionine, or tryptophan residues, the peptide lacks the most common oxidation-sensitive side chains, which simplifies handling compared with many longer peptides.
The proposed relationship between epitalon and pineal function is a central part of its background. Khavinson's group reported that short peptides corresponding to regions of larger pineal proteins could influence gene expression in cells. Epitalon was framed as a synthetic analogue of an active fragment rather than a direct isolation product. Whether the tetrapeptide reproduces the effects of the parent extract is an open question, because comparative studies are limited and the parent extract itself is not a single defined substance.
==== Renal cell carcinoma ==== The VHL (Von Hippel–Lindau) gene encodes a component of an E3 ubiquitin ligase. VHL complex targets a member of the hypoxia-inducible transcription factor family (HIF) for degradation by interacting with the oxygen-dependent destruction domain under normoxic conditions. HIF activates downstream targets such as the vascular endothelial growth factor (VEGF), promoting angiogenesis. Mutations in VHL prevent degradation of HIF and thus lead to the formation of hypervascular lesions and renal tumors.
== Clinical uses == Calcium dobesilate is indicated in states of fragility and altered capillary permeability, e.g. diabetic retinopathy, chronic venous disease and hemorrhoidal disease. In combination with lidocaine or with lidocaine and dexamethasone, the drug enters the composition of preparations for the therapy of hemorrhoidal disease. In association with potassium hydrodex-sulfate enters the composition of adjuvant gels in the treatment of varicose veins. The efficacy of calcium dobesilate has been described in patients with microangiopathies such as diabetic retinopathy and diabetic nephropathy.
The expression host of choice for the expression of many proteins is Escherichia coli as the production of heterologous protein in E. coli is relatively simple and convenient, as well as being rapid and cheap. A large number of E. coli expression plasmids are also available for a wide variety of needs. Other bacteria used for protein production include Bacillus subtilis. Most heterologous proteins are expressed in the cytoplasm of E. coli. However, not all proteins formed may be soluble in the cytoplasm, and incorrectly folded proteins formed in cytoplasm can form insoluble aggregates called inclusion bodies. Such insoluble proteins will require refolding, which can be an involved process and may not necessarily produce high yield. Proteins which have disulphide bonds are often not able to fold correctly due to the reducing environment in the cytoplasm which prevents such bond formation, and a possible solution is to target the protein to the periplasmic space by the use of an N-terminal signal sequence. Another possibility is to manipulate the redox environment of the cytoplasm. Other more sophisticated systems are also being developed; such systems may allow for the expression of proteins previously thought impossible in E. coli, such as glycosylated proteins. The promoters used for these vector are usually based on the promoter of the lac operon or the T7 promoter, and they are normally regulated by the lac operator. These promoters may also be hybrids of different promoters, for example, the Tac-Promoter is a hybrid of trp and lac promoters.
Romania terminated its mission in Iraq and withdrew its last troops on 24 July 2009, among the last countries to do so. The frigate the Regele Ferdinand participated in the 2011 military intervention in Libya. In December 2011, the Romanian Senate unanimously adopted the draft law ratifying the Romania-United States agreement signed in September of the same year that would allow the establishment and operation of a US land-based ballistic missile defence system in Romania as part of NATO's efforts to build a continental missile shield. The Aegis Ashore missile system based at Deveslu became operational in 2016. In 2024, construction work started on expanding the Mihail Kogălniceanu Air Base (RoAF 57th Air Base). The air base is set to become the largest NATO base in Europe after the implementation of a project spanning 20 years.
There are thirteen public universities, a university institute, and a distance university in Portugal. Higher education in Portugal provided by state-run institutions is not free; students must pay a tuition fee. However, the tuition fee is lower than that of private universities. The highest tuition fee allowed by law in public universities is €697 per year as of 2022. Public universities include some of the most selective and demanding higher learning institutions in Portugal.
Sources: en.wikipedia.org
=== Doctoral supervision === Mannervik has supervised more than 60 PhD students and among them Tamas Bartfai, U. Helena Danielson, Mikael Widersten, Per Jemth, Ylva Ivarsson, Vijayakumar Boggaram, M. Kalim Tahir, Usama Hegazy, and Abeer Shokeer have become university professors.
=== Hyperthermia therapy === Hyperthermia therapy is heat treatment for cancer that can be a powerful tool when used in combination with chemotherapy (thermochemotherapy) or radiation for the control of a variety of cancers. The heat can be applied locally to the tumor site, which will dilate blood vessels to the tumor, allowing more chemotherapeutic medication to enter the tumor. Additionally, the tumor cell membrane will become more porous, further allowing more of the chemotherapeutic medicine to enter the tumor cell. Hyperthermia has also been shown to help prevent or reverse "chemo-resistance." Chemotherapy resistance sometimes develops over time as the tumors adapt and can overcome the toxicity of the chemo medication. "Overcoming chemoresistance has been extensively studied within the past, especially using CDDP-resistant cells. In regard to the potential benefit that drug-resistant cells can be recruited for effective therapy by combining chemotherapy with hyperthermia, it was important to show that chemoresistance against several anticancer drugs (e.g. mitomycin C, anthracyclines, BCNU, melphalan) including CDDP could be reversed at least partially by the addition of heat.
==== Nitrogen ==== Nitrogen gas (N2) makes up 78% of the atmosphere and is extremely well mixed over short time-scales, resulting in a homogenous isotopic distribution ideal for use as a reference material. Atmospheric N2 is commonly called AIR when being used as an isotopic reference. In addition to atmospheric N2 there are multiple N isotopic reference materials.
==== Turkey ==== Turkish think tanks are relatively new, having emerged in the 1960s. There are at least 20 think tanks in the country, both independent and supported by government. Many of them are sister organizations of political parties, universities or companies some are independent and others are supported by government. Most Turkish think tanks provide research and ideas, yet they play less important roles in policy making than American think tanks. Turksam, Tasam and the Journal of Turkish Weekly are the leading information sources. The oldest and most influential think tank in Turkey is ESAM (The Center for Economic and Social Research; Turkish: Ekonomik ve Sosyal Araştırmalar Merkezi) which was established in 1969 and has headquarters in Ankara. There are also branch offices of ESAM in Istanbul, Bursa, Konya and elsewhere. ESAM has strong international relationships, especially with Muslim countries and societies. Ideologically it performs policies, produces ideas and manages projects in parallel to Milli Görüş and also influences political parties and international strategies. The founder and leader of Milli Görüş, Necmettin Erbakan, was very concerned with the activities and brainstorming events of ESAM. In The Republic of Turkey, two presidents, four prime ministers, various ministers, many members of the parliament, and numerous mayors and bureaucrats have been members of ESAM. The Turkish Economic and Social Studies Foundation (TESEV) is another leading think tank.
Sources: en.wikipedia.org
The peptide contains four residues in the order alanine, glutamate, aspartate and glycine, abbreviated AEDG. The chain is linear and held together by three peptide bonds. Its calculated mass for the uncharged free form is about 390.3 daltons.
Epithalamin refers to a crude preparation derived from bovine pineal tissue, which contains many components. Epitalon is a single synthetic tetrapeptide identified from that material and produced by chemical synthesis. The two names are sometimes confused because early reports treated the synthetic peptide as an active fragment of the extract.
It has been registered for clinical use in Russia, where it is associated with a small family of short peptides. In most other jurisdictions it is not an approved medicine and is traded as a research chemical. Regulatory status varies by country and changes over time.
Sealed lyophilised powder is normally kept at minus twenty degrees Celsius or below, away from light and moisture. Vials are allowed to reach room temperature before opening to limit condensation. Repeated warming and cooling of the same vial is discouraged.