If you have been reading about peptide analogue 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 2026-06-16. Where a claim depends on a specific study, the study is described rather than over-claimed.
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。
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
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.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C187H291N45O59 | 按主链与 C18 二酸侧链计算 |
| 分子量 | 约 4113.6 道尔顿 | 游离碱形式，随反离子略有差异 |
| 外观 | 白色至类白色冻干粉末 | 具吸湿性，需干燥保存 |
| 溶解性 | 微溶于水，易溶于碱性缓冲液 | 溶解性随 pH 升高而改善 |
| 等电点 | 约 5.4 | 影响缓冲液选择与聚集倾向 |
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.
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.
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.
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.
=== 2009 === A report prepared for the British House of Lords comes to the conclusion that "The precise circumstances surrounding the August 2008 outbreak of the conflict are not yet clear but responsibility for the conflict was shared, in differing measures, by all the parties. There is evidence of a Russian military build-up prior to the August war." On 17 February 2009, the commanding General of the United States Army Europe Carter Ham commented on the training of Georgian military that the United States had trained the Georgian military for Iraq in the previous years, not for the defense of the homeland against Russia. In May 2009, anonymous European diplomat told The New York Times that NATO officials were told in April 2008 by Russia's defense chief that Georgia would be invaded later that year. In July 2009, Alexander Bastrykin, Chairman of the Investigative Committee of the Prosecutor General's Office, told journalists that the investigation of the war was almost complete. However, the guilt of Georgian president Mikheil Saakashvili in instigating the conflict in South Ossetia could not be proven. In September 2009, first president of the Czech Republic Václav Havel, Otto von Habsburg and other European politicians and thinkers wrote: "First, a big power will always find or engineer a pretext to invade a neighbour whose independence it resents. We should remember that Hitler accused the Poles of commencing hostilities in 1939, just as Stalin pinned the blame on the Finns when he invaded their country in 1940.
Complaints about marketed products must be examined, the causes of quality defects must be investigated, and appropriate measures must be taken with respect to the defective products and to prevent recurrence. Good manufacturing practice is recommended with the goal of safeguarding the health of consumers and patients as well as producing quality products. In the United States, a food or drug may be deemed "adulterated" if it has passed all of the specifications tests but is found to be manufactured in a facility or condition which violates or does not comply with current good manufacturing guideline. GMP standards are not prescriptive instructions on how to manufacture products. They are a series of performance based requirements that must be met during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process that both meets business and regulatory needs. Regulatory agencies have recently begun to look at more fundamental quality metrics of manufacturers than just compliance with basic GMP regulations. US-FDA has found that manufacturers who have implemented quality metrics programs gain a deeper insight into employee behaviors that impact product quality.
Bezitramide is an opioid analgesic. Bezitramide itself is a prodrug which is readily hydrolyzed in the gastrointestinal tract to its active metabolite, despropionyl-bezitramide. Bezitramide was discovered at Janssen Pharmaceutica in 1961. It is most commonly marketed under the trade name Burgodin. The drug was pulled from the shelves in the Netherlands in 2004 after fatal overdose cases, including one where a five-year-old child took one tablet from his mother's purse, ate it, and promptly died. Bezitramide is regulated much the same as morphine in all known jurisdictions and is a Schedule II substance under the United States' Controlled Substances Act of 1970, with an ACSCN of 9800 and zero annual manufacturing quota. However, as of May 2021, it has never been marketed in the United States.
Sources: en.wikipedia.org
=== Entomopathic viruses === Of the many types of entomopathic viruses, only baculaviruses are used commercially, and are each specific for their target insect. They have to be grown on insects, so their production is labour-intensive.
== Mechanism == Obstructive sleep apnea The causes of obstructive sleep apnea are complex and individualized, but typical risk factors include narrow pharyngeal anatomy and craniofacial structure. When anatomical risk factors are combined with non-anatomical contributors such as an ineffective pharyngeal dilator muscle function during sleep, unstable control of breathing (high loop gain), and premature awakening to mild airway narrowing, the severity of the OSA rapidly increases as more factors are present. When breathing is paused due to upper airway obstruction, carbon dioxide builds up in the bloodstream. Chemoreceptors in the bloodstream note the high carbon dioxide levels. The brain is signaled to awaken the person, which clears the airway and allows breathing to resume. Breathing normally will restore oxygen levels and the person will fall asleep again. This carbon dioxide build-up may be due to the decrease of output of the brainstem regulating the chest wall or pharyngeal muscles, which causes the pharynx to collapse. As a result, people with sleep apnea experience reduced or no slow-wave sleep and spend less time in REM sleep. Central sleep apnea There are two main mechanism that drive the disease process of CSA, sleep-related hypoventilation and post-hyperventilation hypocapnia. The most common cause of CSA is post-hyperventilation hypocapnia secondary to heart failure. This occurs because of brief failures of the ventilatory control system but normal alveolar ventilation.
=== Variation === The lobes of the lung are subject to anatomical variations. A horizontal interlobar fissure was found to be incomplete in 25% of right lungs, or even absent in 11% of all cases. An accessory fissure was also found in 14% and 22% of left and right lungs, respectively. An oblique fissure was found to be incomplete in 21% to 47% of left lungs. In some cases a fissure is absent, or extra, resulting in a right lung with only two lobes, or a left lung with three lobes. A variation in the airway branching structure has been found specifically in the central airway branching. This variation is associated with the development of COPD in adulthood.
A substance can often be classified as an acid or a base. There are several different theories which explain acid–base behavior. The simplest is Arrhenius theory, which states that an acid is a substance that produces hydronium ions when it is dissolved in water, and a base is one that produces hydroxide ions when dissolved in water. According to Brønsted–Lowry acid–base theory, acids are substances that donate a positive hydrogen ion to another substance in a chemical reaction; by extension, a base is the substance which receives that hydrogen ion. A third common theory is Lewis acid–base theory, which is based on the formation of new chemical bonds. Lewis theory explains that an acid is a substance which is capable of accepting a pair of electrons from another substance during the process of bond formation, while a base is a substance which can provide a pair of electrons to form a new bond. There are several other ways in which a substance may be classified as an acid or a base, as is evident in the history of this concept. Acid strength is commonly measured by two methods. One measurement, based on the Arrhenius definition of acidity, is pH, which is a measurement of the hydronium ion concentration in a solution, as expressed on a negative logarithmic scale. Thus, solutions that have a low pH have a high hydronium ion concentration and can be said to be more acidic.
Sources: en.wikipedia.org
Drive to improve quality of patient care Need to contain burgeoning healthcare costs Improve accessibility and portability of patient records Better source data for epidemiological studies Before health records can be successfully communicated and stored there must be a fundamental agreement on the definition for each individual piece of information. Terminology solutions for describing such "concepts" currently include (but are not limited to) SNOMED CT, LOINC and the NPU. Key benefits conferred by the NPU terminology include:
=== Cancer treatment === Some preclinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment. However, other studies do not show a correlation between cancer survival and beta blocker use. Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer.
Hydroxynorketamine (HNK), or 6-hydroxynorketamine, is a minor metabolite of the anesthetic, dissociative, and antidepressant drug ketamine. It is formed by hydroxylation of the intermediate norketamine, another metabolite of ketamine. As of late 2019, (2R,6R)-HNK is in clinical trials for the treatment of depression. The major metabolite of ketamine is norketamine (80%). Norketamine is secondarily converted into 4-, 5-, and 6-hydroxynorketamines (15%), mainly HNK (6-hydroxynorketamine). Ketamine is also transformed into hydroxyketamine (5%). As such, bioactivated HNK comprises less than 15% of a dose of ketamine.
Sources: en.wikipedia.org
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。
胰岛素释放需要细胞内环腺苷酸与钙信号升高，同时依赖葡萄糖代谢产生的协同信号。血糖水平较低时协同信号不足，分泌增强有限。这一机制在降糖效果与低血糖风险之间提供了缓冲。
白蛋白结合是主要原因，它减少肾小球滤过并保护分子免受蛋白酶降解。序列修饰带来的酶解抵抗同样不可忽略，二者共同作用。脂肪链的疏水性还会影响组织分布，但其对总半衰期的贡献程度仍在研究之中。
Native GLP-1 is a short-lived peptide cleared within one to two minutes by dipeptidyl peptidase-4 and related enzymes. Semaglutide keeps the receptor-binding backbone but adds substitutions and a lipid chain. These changes block the main cleavage site and allow reversible albumin binding, extending the half-life to roughly 165 hours.