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Updated 2025-10-19. Numbers and descriptions here follow the published literature rather than marketing material.
Ipamorelin 是一种合成五肽，序列为 Aib-His-D-2-Nal-D-Phe-Lys-NH2，分子式 C38H49N9O5，游离碱分子量约 711.85 g/mol。它属于生长激素促分泌素（GHS）家族，作用靶点是胃饥饿素受体 GHS-R1a。该化合物由诺和诺德的研究团队在二十世纪九十年代末报道，设计目标是提高对生长激素释放的选择性。C 端酰胺化与 N 端 Aib 残基是两个用于抵抗肽酶降解的结构特征。
在 GHS 家族中，早期肽类如 GHRP-6 与 GHRP-2 会同时促进生长激素、皮质醇与催乳素的释放，并明显增加食欲。Ipamorelin 在动物与早期人体研究中表现出对生长激素释放的相对选择性，对上述其他激素的影响较小。这种差异通常归因于受体结合模式与下游信号偏向的不同，而完整的分子解释仍有待补充。需要区分的是，选择性是研究观察中的相对程度，并非绝对界限。
从用途定位看，ipamorelin 目前主要以研究用肽的身份被讨论，未见主要药品监管机构将其批准为治疗药物。市售材料通常标注仅供研究使用，不得用于人体或诊断程序。文献中它常与生长激素促分泌素、GHS-R1a 激动剂、胃饥饿素拟似物等表述并列出现。既有研究的样本量普遍偏小，因此对其效应强度与一致性的描述应保持谨慎。
The compound was developed at Novo Nordisk during the 1990s as part of a programme seeking secretagogues with improved selectivity. It was described in the peer-reviewed literature in 1998 alongside related pentapeptides from the same series. Investigators advanced it because it raised growth hormone output in animal models while leaving other pituitary hormones comparatively unaffected. The development code NNC 26-0161 appears in earlier reports, and ipamorelin later became the common designation in published work.
Selectivity is the property most often attached to this peptide. Published animal and early human studies record increases in growth hormone release after administration, with adrenocorticotropic hormone and cortisol responses remaining small by comparison. Effects on appetite-related pathways also appear weaker than those reported for several earlier secretagogues. Reviews that compare members of the growth hormone secretagogue family cite these findings frequently, though the receptor-level explanation for the selectivity continues to be debated rather than settled.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C38H49N9O5 | 五肽，C 端酰胺化 |
| 分子量 | 约 711.85 g/mol | 游离碱形式 |
| 外观 | 白色至类白色冻干粉 | 研究用材料的常见形态 |
| 溶解性 | 溶于水及 DMSO 等极性溶剂 | 建议现配现用 |
| 储存温度 | -20 °C 或更低 | 干燥、避光、限制冻融次数 |
Ipamorelin is a synthetic pentapeptide that acts as an agonist at the ghrelin receptor, also called the growth hormone secretagogue receptor type 1a. Its sequence incorporates non-natural residues, which slows enzymatic breakdown relative to short native peptides. In laboratory and early clinical work the compound is described as a selective growth hormone secretagogue because it raises growth hormone with comparatively little effect on other pituitary outputs. The degree to which that selectivity holds across species and dosing regimens remains an open question in the published literature.
Signal transduction begins when the peptide binds GHSR-1a on pituitary somatotrophs. The receptor couples to Gq/11 proteins, activating phospholipase C, which cleaves phosphatidylinositol bisphosphate into inositol trisphosphate and diacylglycerol. Inositol trisphosphate releases calcium from intracellular stores, and the resulting rise in cytosolic calcium drives growth hormone vesicle fusion. Concurrent Gs coupling and cyclic AMP elevation have also been reported, and the relative contribution of each arm to the overall secretory response is not fully settled.
Structural features distinguish the molecule from earlier secretagogues. An alpha-aminoisobutyric acid residue near the N-terminus and a D-naphthylalanine substitution increase receptor affinity, while C-terminal amidation improves resistance to exopeptidases. These modifications are associated with reduced stimulation of appetite and of the hypothalamic-pituitary-adrenal axis compared with hexarelin or growth hormone releasing peptide-6. Whether the same profile applies at every dose level studied is a matter of ongoing investigation rather than settled consensus.
Lyophilized ipamorelin is generally held at minus twenty degrees Celsius or colder, protected from light and moisture. In solution the peptide is less stable, and degradation proceeds through hydrolysis of the amide backbone, oxidation of the histidine residue, and aggregation. Repeated freeze-thaw cycles accelerate these processes, so dividing material into single-use aliquots before freezing is common practice in research settings. Buffered formulations near neutral pH tend to show the slowest degradation, while strongly acidic or basic conditions raise hydrolysis rates. Stability data specific to ipamorelin are sparse, and much guidance is extrapolated from other short peptides.
Quality control for research-grade ipamorelin is not governed by a single harmonized pharmacopeial monograph, so certificates of analysis vary between suppliers. Common tests include appearance, solubility, water content, peptide content by quantitative amino acid analysis, and residual counterion measurement. Independent verification by an outside laboratory is often used to confirm identity and purity claims. Salt form, counterion content, and residual solvent levels are frequently unspecified, which complicates direct comparison between lots and leaves reproducibility partly unresolved.
Identity and purity assessment of ipamorelin relies mainly on reversed-phase high-performance liquid chromatography with ultraviolet detection near 214 nanometers, a wavelength where the peptide backbone absorbs. Mass confirmation is typically obtained by electrospray ionization mass spectrometry or by liquid chromatography coupled to mass spectrometry, comparing the observed mass with the calculated value. Amino acid analysis and peptide mapping after enzymatic digestion can confirm the sequence. Impurity profiles include deletion peptides, truncated fragments, and oxidation products, reported as relative area percentages.
Lyophilized material is generally held at minus twenty degrees Celsius or lower, protected from moisture and light. Repeated excursions to room temperature cause condensation inside the vial and gradual moisture uptake, both of which shorten shelf life. Containers should be allowed to equilibrate before opening so that water does not condense on the solid. Dividing a batch into single-use aliquots reduces freeze-thaw cycling. Solid peptide handled this way is usually considered stable for months to years, while the same material in solution degrades on a much shorter timescale.
Common solvents for laboratory work include water, buffered saline, and dimethyl sulfoxide. Once dissolved, the peptide is exposed to hydrolysis and oxidation, and alkaline conditions accelerate breakdown. Low-binding plasticware and the addition of a carrier protein reduce losses to container surfaces, which can otherwise be substantial at low concentrations. Solutions are typically kept cold and used within days. Investigators working with the compound generally prepare fresh working dilutions rather than storing dilute stocks, and they avoid repeated warming of the same vial.
Reversed-phase high-performance liquid chromatography is the standard method for purity assessment, most often on a C18 column with a water and acetonitrile gradient and trifluoroacetic acid or formic acid as an ion-pairing agent. Mass spectrometry by electrospray or matrix-assisted laser desorption confirms the expected mass and reveals truncated or modified sequences. Amino acid analysis and sequencing provide orthogonal structural evidence. Typical impurities include deletion sequences, oxidized products, and dimeric species. Detection wavelength, usually 214 or 220 nanometers, should be reported because response factors differ between peptides.
=== Indicator plants === Certain species of plants are considered indicators of high selenium content of the soil, since they require high levels of selenium to thrive. The main selenium indicator plants are Astragalus species (including some locoweeds), prince's plume (Stanleya sp.), woody asters (Xylorhiza sp.), and false goldenweed (Oonopsis sp.)
== Classification == The MEROPS protease classification system counts 16 superfamilies (as of 2013) each containing many families. Each superfamily uses the catalytic triad or dyad in a different protein fold and so represent convergent evolution of the catalytic mechanism. The majority belong to the S1 family of the PA clan (superfamily) of proteases. For superfamilies, P: superfamily, containing a mixture of nucleophile class families, S: purely serine proteases. superfamily. Within each superfamily, families are designated by their catalytic nucleophile, (S: serine proteases).
== Disease relevance == CHS, as the first committed step in the flavonoid pathway, facilitate production of flavanoids, isoflavonoid-type phytoalexins and other metabolites to protect the plant from stress. CHS expression is also involved in the salicyclic acid defense pathway. Being aromatic compounds, flavonoids strongly absorb UV light through a photoreceptor-mediated mechanism which effectively protects the plants from DNA damage. CHS is involved in a broader, more general phenylpropanoid pathway which serve as precursors to a range of plant metabolites important to human health such as antioxidants, anti-inflammatory agents, antiallergens, and even antioncogenic products.
To make the proteins accessible to antibody detection, they are moved from within the gel onto a membrane, a solid support, which is an essential part of the process. There are two types of membrane: nitrocellulose (NC) or polyvinylidene difluoride (PVDF). NC membrane has high affinity for protein and its retention abilities. However, NC is brittle, and does not allow the blot to be used for re-probing, whereas PVDF membrane allows the blot to be re-probed. The most commonly used method for transferring the proteins is called electroblotting. Electroblotting uses an electric current to pull the negatively charged proteins from the gel towards the positively charged anode, and into the PVDF or NC membrane. The proteins move from within the gel onto the membrane while maintaining the organization they had within the gel. An older method of transfer involves placing a membrane on top of the gel, and a stack of filter papers on top of that. The entire stack is placed in a buffer solution which moves up the paper by capillary action, bringing the proteins with it. In practice this method is not commonly used due to the lengthy procedure time. As a result of either transfer process, the proteins are exposed on a thin membrane layer for detection. Both varieties of membrane are chosen for their non-specific protein binding properties (i.e. binds all proteins equally well). Protein binding is based upon hydrophobic interactions, as well as charged interactions between the membrane and protein.
Sources: en.wikipedia.org
Hudson, John, Normans, BBC. Dudo of St. Quentin, Gesta Normannorum, The orb, English translation. Breve Chronicon Northmannicum (in Latin), Storia online. The Normans (PDF), Jersey heritage trust, archived from the original (PDF) on 26 March 2009. The Normans in Italy (in Italian), MondoStoria, archived from the original on 1 September 2017, retrieved 14 May 2015. Freeman, Edward Augustus (1911). "Normans" . Encyclopædia Britannica. Vol. 19 (11th ed.). pp. 751–756.
== Structure == Several structures of glyoxalase I have been solved. Four structures of the human form have been published, with PDB accession codes PDB: 1BH5, PDB: 1FRO, PDB: 1QIN, and PDB: 1QIP. Five structures of the Escherichia coli form have been published, with accession codes PDB: 1FA5, PDB: 1FA6, PDB: 1FA7, PDB: 1FA8, and PDB: 1F9Z. Finally, one structure of the trypanothione-specific version from Leishmania major has been solved, PDB: 2C21. In all these cases, the quaternary structure of the biological unit is a domain-swapped dimer, in which the active site and the 8-stranded beta sheet secondary structure is formed from both subunits. However, in yeast such as Saccharomyces cerevisiae, the two subunits have fused into a single monomer of double size, through gene duplication. Each half of the structural dimer is a sandwich of 3-4 alpha helices on both sides of an 8-stranded antiparallel beta sheet; the dimer interface is largely composed of the face-to-face meeting of the two beta sheets. The tertiary and quaternary structures of glyoxalase I is similar to those of several other types of proteins. For example, glyoxalase I resembles several proteins that allow bacteria to resist antibiotics such as fosfomycin, bleomycin and mitomycin. Likewise, the unrelated enzymes methylmalonyl-CoA epimerase, 3-demethylubiquinone-9 3-O-methyltransferase and numerous dioxygenases such as biphenyl-2,3-diol 1,2-dioxygenase, catechol 2,3-dioxygenase, 3,4-dihydroxyphenylacetate 2,3-dioxygenase and 4-hydroxyphenylpyruvate dioxygenase all resemble glyoxalase I in structure.
This complication may manifest as systemic infections, such as sepsis, or as localized outbreaks, such as Herpes simplex, shingles, or other members of the Herpesviridea. The risk of illness and death can be reduced by taking common antibiotics such as quinolones or trimethoprim/sulfamethoxazole before any fever or sign of infection appears. Quinolones show effective prophylaxis mainly with hematological cancer. However, in general, for every five people who are immunosuppressed following chemotherapy who take an antibiotic, one fever can be prevented; for every 34 who take an antibiotic, one death can be prevented. Sometimes, chemotherapy treatments are postponed because the immune system is suppressed to a critically low level. In Japan, the government has approved the use of some medicinal mushrooms like Trametes versicolor, to counteract depression of the immune system in people undergoing chemotherapy. Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by chemotherapy. The drug is given before chemotherapy to protect bone marrow function.
Sources: en.wikipedia.org
Dance in India draws heavily on Indian classical dance traditions. Many of these in turn arose in temples or other religious contexts. However, their sponsorship and promotion have continued in secular, modern India. India also has local and modern dance traditions. Whether a dance is classical is determined by the Sangeet Natak Academi, the Indian government's organisation for performing arts. Although more dances could perhaps meet the criteria for classical, the Akademi has chosen eight.
Their large size and fearsome reputation make them popular zoo exhibits. In the wild, their range has been reduced by human encroachment and is likely to contract further from the effects of climate change; hence, they are listed as Endangered by the IUCN Red List. They are protected under Indonesian law, and the Komodo National Park was founded in 1980 to aid protection efforts. In the Komodo language, the dragons are called sebae 'twins' out of a traditional belief by the Komodo people that they share the same spiritual mother as the dragons. Meanwhile, the Baar people, who speak the Baar dialect of Riung language, call the Komodo dragon mbau.
=== New generation fuel === The aim of Guy Reinaud's project is to reply to the needs, in renewable domestic energy, of a population of 2 billion individuals living in the tropical regions of Africa, Latin America and Asia, and at the same time fighting against deforestation and climatic changes. The proposed solution is biomass charcoal as a source of renewable energy - patented and developed by Pro-Natura International. Biomass charcoal produces domestic energy from non-upgraded biomass, other than wood, in particular agricultural residues non-consumed by animals. By reducing the dependence on wood, biomass charcoal protects forests and as a consequence fights against desertification. Moreover, the energy produced by biomass charcoal is equal to that of wood charcoal for a sales price per kilo 50% cheaper.
== Traffic tunnels == Traffic tunnels may be traversed by vehicles carrying flammable goods, such as petrol, liquefied petroleum gas and other hydrocarbons, which are known to cause a very rapid temperature rise and high ultimate temperatures in case of a fire (see the hydrocarbon curves in fire-resistance rating). Where hydrocarbon transports are permitted in tunnel construction and operations, accidental fires may occur, resulting in the need for fireproofing of traffic tunnels with concrete linings.
Sources: en.wikipedia.org
两者都是 GHS-R1a 激动剂，但 ipamorelin 在研究中显示出更高的生长激素释放选择性。早期资料显示它对皮质醇、催乳素与食欲的刺激弱于 GHRP-6。这些差异是相对程度，而非绝对区分。
公开资料中它主要以研究用肽的形式出现，未获主要监管机构批准用于治疗。可得材料通常标注仅供研究使用。任何临床用途的宣称都缺少监管依据。
序列中的 Aib 与 D-2-Nal 等非天然残基可提高对肽酶的抵抗能力，并影响受体结合的构象。这类修饰在合成肽设计中较为常见。它们也使常规氨基酸分析需要额外步骤才能确认序列。
Aib 即 α-氨基异丁酸，是一种非蛋白质源氨基酸，其侧链为两个甲基。它在肽链中倾向于诱导螺旋构象并限制骨架的柔性。这种刚性被认为有助于抵抗蛋白酶切割。