The short version of GLP-1 类似物 fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-02-27. Anything still debated is marked as such rather than presented as settled.
Pharmacological activity arises from agonism at the glucagon-like peptide-1 receptor, a G protein-coupled receptor expressed in the pancreas, the gastrointestinal tract, and the brainstem. Receptor activation raises intracellular cyclic adenosine monophosphate and enhances insulin release in a glucose-dependent manner, an effect that diminishes when blood glucose concentration is low. Other effects include slowed gastric emptying and hypothalamic satiety signalling. These pathways are described well. Receptor desensitisation rates across tissues, relative to the endogenous hormone, are still under investigation, and reported findings differ between laboratories.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
Semaglutide is a synthetic peptide of thirty-one amino acids that shares roughly ninety-four percent sequence identity with human glucagon-like peptide-1. Two substitutions resist enzymatic cleavage by dipeptidyl peptidase-4, and a fatty diacid side chain attached through a linker promotes binding to serum albumin. That albumin binding slows renal clearance and extends the circulating half-life from minutes to approximately one week. The structural changes are well established in the published literature. Whether the same modifications affect receptor signalling bias in ways that matter clinically remains an open question.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
Storage at minus 20 degrees Celsius or lower in a desiccated container preserves the peptide for extended periods, while working solutions are commonly held at two to eight degrees Celsius for short intervals. Light exposure and repeated freeze-thaw cycles accelerate degradation, so dividing material into single-use aliquots is generally recommended. Adsorption to glass and plastic surfaces can lower the measured concentration of dilute solutions, particularly below one milligram per millilitre. The degradation routes most often reported for GLP-1 analogues are deamidation, methionine oxidation, and backbone hydrolysis. Relative rates under specific conditions are frequently described only for individual formulations.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 or 280 nanometres is widely used to assess purity and to resolve related impurities. Liquid chromatography coupled to mass spectrometry confirms identity through the protonated molecular ion and fragment ions formed in tandem experiments. Capillary electrophoresis and peptide mapping after enzymatic digestion supply complementary information on charge variants and modification sites. Circular dichroism and nuclear magnetic resonance can report on secondary structure in solution. Absolute quantification usually depends on an external standard, and reported purity depends on the detection wavelength and integration parameters chosen.
Lyophilised material appears as a white to off-white cake or powder that is hygroscopic, and containers are usually equilibrated to room temperature before opening to limit condensation. Dissolution is performed in water, phosphate-buffered saline, or a mildly alkaline buffer, since solubility rises above neutral pH. Gentle inversion or low-speed mixing is preferred, because vigorous vortexing can promote surface denaturation and aggregation. Complete dissolution may require several minutes, and brief sonication is sometimes applied. Passing the solution through a 0.22 micrometre membrane removes particulates but does not by itself sterilise the liquid.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
==== 2023 Rugby World Cup ==== 9 September – Ireland 82–8 Romania, Nouveau Stade de Bordeaux, Bordeaux. 16 September – Ireland 59–16 Tonga, Stade de la Beaujoire, Nantes. 23 September – South Africa 8–13 Ireland, Stade de France, Saint-Denis. 7 October – Ireland 36–14 Scotland, Saint-Denis. 14 October – Ireland 24–28 New Zealand. Ireland were eliminated by New Zealand in the quarter final.
Too high a concentration of the organic may cause the micelle to disperse, as it relies on hydrophobic effects for its formation. The maximum concentration of organic depends on the organic solvent itself, and on the micelle. This information is generally not known precisely, but a generally accepted practice is to keep the volume percentage of organic below 15–20%.
== Physiology == A subunits of human factor XIII are made primarily by platelets and other cells of bone marrow origin. B subunits are secreted into blood by hepatocytes. A and B units combine within blood to form heterotetramers of two A units and two B units. Blood plasma concentration of the heterotetramers is 14–48 mg/L and half-life is 9–14 days. A clot that has not been stabilized by FXIIIa is soluble in 5 mol/L urea, while a stabilized clot is resistant to this phenomenon.
Sources: en.wikipedia.org
Hunger has been a perennial human problem. However, until the early 20th century, there was relatively little awareness of the qualitative aspects of malnutrition. Throughout history, various peoples have known the importance of eating certain foods to prevent symptoms now associated with malnutrition. Yet such knowledge appears to have been repeatedly lost and then re-discovered. For example, the ancient Egyptians reportedly knew the symptoms of scurvy. Much later, in the 14th century, Crusaders sometimes used anti-scurvy measures – for example, ensuring that citrus fruits were planted on Mediterranean islands, for use on sea journeys. However, for several centuries, Europeans appear to have forgotten the importance of these measures. They rediscovered this knowledge in the 18th century, and by the early 19th century, the Royal Navy was issuing frequent rations of lemon juice to every crewman on their ships. This massively reduced scurvy deaths among British sailors, which in turn gave the British a significant advantage in the Napoleonic Wars. Later on in the 19th century, the Royal Navy replaced lemons with limes (unaware at the time that lemons are far more effective at preventing scurvy).
The oldest known parish register in Paris belongs to the parish of Saint-Jean-en-Grève. In agenda format and written in Latin, it covers the period from April 1515 to November 1521. Registers of baptisms were opened as early as 1525 in the parishes of Saint-André-des-Arts and Saint-Jacques-la-Boucherie. The first burial registers, from Saint-Josse and Saint-Landry, date back to 1527. In August 1539, Francis I issued the Ordinance of Villers-Cotterêts, requiring parish priests to keep a register of baptisms conducted in their church, written in French (Article 51):
=== Proton vs. hydride transfer === Glyoxalase I was originally believed to operate by the transfer of a hydride, which is a proton surrounded by two electrons (H–). In this, it was thought to resemble the classic Cannizzaro reaction mechanism, in which the attack of a hydroxylate on an aldehyde renders it into a tetravalent alcohol anion; this anion donates its hydrogens to a second aldehyde, forming a carboxylic acid and an alcohol. (In effect, two identical aldehydes reduce and oxidize each other, leaving the net oxidation state the same.) In glyoxalase I, such a hydride-transfer mechanism would work as follows. The attack of the glutathione would leave a charged O– and the aldehyde hydrogen bound to C1. If the carbonyl oxygen of C2 can secure a hydrogen from an obliging acidic sidechain of the enzyme, forming an alcohol, then the hydrogen of C1 might simultaneously slide over with its electrons onto C2 (the hydride transfer). At the same time, the extra electron on the oxygen of C1 could reform the double bond of the carbonyl, thus giving the final product. An alternative (and ultimately correct) mechanism using proton (H+) transfer was put forward in the 1970s. In this mechanism, a basic sidechain of the enzyme abstracts the aldehyde proton from C1; at the same time, a proton is added to the oxygen of C2, thus forming a enediol. The ene means that a double bond has formed between C2 and C1, from the electrons left behind by the abstraction of the aldehyde proton; the diol refers to the fact that two alcohols have been made of the initial two carbonyl groups.
Between 30 and 40 percent of people undergoing chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), a progressive, enduring, and often irreversible condition, causing pain, tingling, numbness and sensitivity to cold, beginning in the hands and feet and sometimes progressing to the arms and legs. Chemotherapy drugs associated with CIPN include thalidomide, epothilones, vinca alkaloids, taxanes, proteasome inhibitors, and the platinum-based drugs. Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount consumed and whether the person already has peripheral neuropathy. Though the symptoms are mainly sensory, in some cases motor nerves and the autonomic nervous system are affected. CIPN often follows the first chemotherapy dose and increases in severity as treatment continues, but this progression usually levels off at completion of treatment. The platinum-based drugs are the exception; with these drugs, sensation may continue to deteriorate for several months after the end of treatment. Some CIPN appears to be irreversible. Pain can often be managed with drug or other treatment but the numbness is usually resistant to treatment.
Sources: en.wikipedia.org
The World Health Organization in 1987 found that comfortable indoor temperatures of 18–24 °C (64–75 °F) were not associated with health risks for healthy adults with appropriate clothing, humidity, and other factors. For infants, elderly, and those with significant health problems, a minimum of 20 °C (68 °F) was recommended. Temperatures lower than 16 °C (61 °F) with humidity above 65% were associated with respiratory hazards including allergies. The WHO's 2018 guidelines give a strong recommendation that a minimum of 18 °C (64 °F) is a "safe and well-balanced indoor temperature to protect the health of general populations during cold seasons". A higher minimum temperature may be necessary for vulnerable groups including children, the elderly, and people with cardiorespiratory disease and other chronic illnesses. However, the recommendation regarding risk of exposure to high indoor temperatures is only "conditional". Minimal-risk high temperatures range from about 21 to 30 °C (70 to 86 °F) depending on the region, with maximum acceptable temperatures between 25 and 32 °C (77 and 90 °F).
The Constituent Assembly of India chose the official language of India's federal government in September 1949 after three years of debate between two opposing camps. Hindi language protagonists wanted Hindi in the Devanagari script to be the sole "national language" of India whereas delegates from South India preferred English to have a place in the Constitution. The compromise reached declared (i) Hindi to be the "official language" of India's federal government; (ii) English to be an associate official language for 15 years during which Hindi's formal lexicon would be developed; and (iii) the international form of Hindu–Arabic numerals to be the official numerals. The compromise resolution became articles 343–351 of India's constitution, which came into effect on 26 January 1950. In 1965, after bitter opposition from South India to Hindi becoming the sole official language, a compromise was reached whereby English would continue to be an "associate official language" indefinitely. The Eighth Schedule of India's Constitution also recognises 22 languages, including Hindi but not English, which the government must develop. These are sometimes called "scheduled languages". This list includes major regional languages, but also others—such as Sanskrit, which no longer has first language speakers in India, and Urdu, which is not region-specific—because of their value to India's cultural heritage. In 1950, there were 14 scheduled languages: Assamese, Bengali, Gujarati, Hindi, Kannada, Kashmiri, Malayalam, Marathi, Oriya, Punjabi, Sanskrit, Tamil, Telugu and Urdu.
In March 2020, the Roche Diagnostics division reached a significant milestone with the FDA-approval of its high-volume Sars-CoV-2 diagnostic test, capable of analysing 1,400-8,800 samples within 24h on the proprietary Cobas 6800/8800 molecular testing system. In September, the business acquired Ireland-based Inflazome, for €380 million, gaining control of its NLRP3 inflammasome inhibitors. In March 2021, Roche announced it would acquire GenMark Diagnostics for $1.8 billion. Under the terms of agreement, Genmark diagnostics will become a subsidiary and the principal operations will continue to remain in Carlsbad, California. In September, the company announced it would acquire German biotech group, TIB Molbiol, enhancing its molecular diagnostics operations. In September 2022, Roche acquired Good Therapeutics at a cost of $250M for its PD1-regulated IL-2 receptor agonist program. In July 2023, Roche partnered with Alnylam Pharmaceuticals in a deal worth $2.8 billion for the development of a hypertension drug. In December 2023, Roche acquired Carmot Therapeutics, an anti-obesity drug developer, for $2.7 billion. In October 2023, Monte Rosa Therapeutics and Roche signed a strategic cooperation and licensing agreement for the discovery and development of molecular adhesive degradators (MGD) to combat cancer and neurological diseases. The partnership includes Monte Rosa's QuEENT discovery engine and Roche Holding expertise.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
It belongs to the incretin mimetic class and acts as a long-acting glucagon-like peptide-1 receptor agonist. The class includes several peptides with different half-lives and routes of administration.