The short version of receptor agonist fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-11-05 and is reviewed periodically as new material appears.
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.
Two principal therapeutic variants exist under separate regulatory filings, one indicated for glycemic control in type 2 diabetes and one for chronic weight management. Both use the same active molecule; differences lie in formulation strength, titration schedule, and labeling. Regulatory agencies in the United States and European Union approved injectable forms in 2017 and 2018 respectively. An oral tablet formulation received approval later, using a carrier molecule to enhance absorption across the gastric epithelium. Labeling differs by jurisdiction and by indication.
The distinction between established facts and open questions matters here. That the peptide binds the GLP-1 receptor and stimulates insulin release in a glucose-dependent manner is well documented. How individual variability in receptor density, gastric emptying rate, and gut microbiome composition shapes response remains an active research area. Long-term outcomes beyond five years of continuous use are not yet fully characterized in published trials, and several extension studies are ongoing.
| 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 |
Stability studies examine how temperature, pH, and moisture influence degradation rates over time. In aqueous solution, hydrolysis and deamidation accelerate as pH moves away from mildly acidic conditions. Light exposure and residual metal ions can also trigger oxidation of susceptible residues. Accelerated aging at elevated temperature is used to estimate shelf life, though extrapolation to room temperature carries uncertainty because individual degradation pathways do not always scale predictably.
Lyophilized semaglutide powder is typically held at minus twenty degrees Celsius for long-term storage. At that temperature, solid-state degradation reactions proceed slowly and the peptide remains intact for extended periods. Repeated freeze-thaw cycles are best avoided because they promote aggregation and can shift the proportion of monomeric peptide present. Working aliquots are often prepared so that each portion is thawed only once, and desiccant is placed inside the vial to limit moisture uptake.
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。
Semaglutide belongs to the glucagon-like peptide-1 receptor agonist class, a group of synthetic peptides that imitate an incretin hormone released by intestinal L cells after food intake. Native GLP-1 circulates for only a few minutes because dipeptidyl peptidase-4 cleaves it rapidly. The hormone acts on pancreatic islets, the gastrointestinal tract, and several brain regions. Because the natural peptide is short-lived, development work concentrated on analogues that keep receptor activity while resisting enzymatic breakdown and renal clearance.
The semaglutide sequence is a 31-residue analogue of human GLP-1, altered at three positions relative to the parent hormone. Aminoisobutyric acid replaces alanine at position 8, arginine replaces lysine at position 34, and a lipophilic diacid is attached to lysine 26 through a short linker. These features are reported consistently in the structural literature. The position 8 substitution blocks recognition by dipeptidyl peptidase-4, while the attached chain drives strong, reversible association with a carrier protein in blood.
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.
== Medical uses == Gallium (68Ga) gozetotide is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer. Ga 68 PSMA-11 injections are used for PET imaging of prostate-specific membrane antigen (PSMA) positive lesions in males with prostate cancer. It can be given for the patients with suspected metastasis, and the candidates with initial definitive therapy.
The Nintendo Switch version received "mixed or average" reviews according to review aggregator Metacritic. Daniel Tack of Game Informer praised the game's music, mechanics, and narrative, but did not give the game an official rating. Alice Bell of Rock Paper Shotgun described the game as "extremely odd" and "extremely terrifying". Russell Troxel praised the game, stating that it is "worth every penny they’re asking". On consoles, the game was generally positively noted for its narrative and voice acting, but was criticized for its performance issues, confusing gameplay and sluggish interface. Shaun Musgrave, in his review on TouchArcade, said the Nintendo Switch version has "fantastic characters and sublime music" with a new Japanese voiceover option. He found the console version's stability issues a downgrade from the PC counterpart, which he noted was already poorly optimized, and commented its text size is too small to be playable. Charlie Wacholz of Nintendo Life gave it a negative review, criticizing confusing gameplay, clunky menus, and performance issues. He found the game difficult to play in longer sessions due to its text being almost illegible on screen, and compare its trial-and-error gameplay to "a mild bout of Stockholm Syndrome". He scored it a 4 out of 10. Kazuma Hashimoto from Siliconera left a mixed review, calling its voice acting "top notch" and enjoying its turn-based battle system for its complexity.
Richard F. Edlich (January 19, 1939, New York City, New York – December 25, 2013, Brush Prairie, Washington) was a Professor Emeritus of Plastic Surgery, Biomedical Engineering and Emergency Medicine at the University of Virginia Health System. His basic clinical and research interests focused on improving the safety and outcome of wound care in emergency medicine and surgery.
=== Multi-material printing === The color, flavor and texture of food are of crucial importance when fabricating an edible product, thus in most cases it is required that a food printer supports multi-material printing. The current available 3D food printers are limited to using a few different materials due to the challenge of developing multiple extruder capabilities. This limits the variety of food products that can be 3D printed, leaving out complex dishes that require a lot of different materials.
== Scientific analysis == Sindonology (from the Greek σινδών—sindon, the word used in the Gospel of Mark to describe the type of the burial cloth of Jesus) is the formal study of the Shroud. The Oxford English Dictionary cites the first use of this word in 1964: "The investigation ... assumed the stature of a separate discipline and was given a name, sindonology", but also identifies the use of "sindonological" in 1950 and "sindonologist" in 1953. Secondo Pia's 1898 photographs of the shroud allowed the scientific community to begin to study it. A variety of scientific theories regarding the shroud have since been proposed, based on disciplines ranging from chemistry to biology and medical forensics to optical image analysis. The scientific approaches to the study of the Shroud fall into three groups: material analysis (both chemical and historical), biology and medical forensics and image analysis.
Sources: en.wikipedia.org
South Africa manufactured several complete nuclear weapons in the 1980s, but during the 1990s, it became the only country to eliminate its domestically produced nuclear arsenal, and abandon further nuclear weapon production. Nuclear weapons have been detonated on over 2,000 occasions for various testing purposes. Countries have increased their readiness to carry out strategic and tactical nuclear attacks in response to intensifying conflicts, including the Korean War, First and Second Taiwan Strait Crises, Cuban Missile Crisis, Vietnam War, Sino-Soviet border conflict, Yom Kippur War, Gulf War, and Russo-Ukrainian war. The 1962 Cuban Missile Crisis, between the nuclear superpowers of the U.S. and Soviet Union, is often considered the closest call with a nuclear exchange and possible World War III. Additionally, nuclear attack early warning systems have sometimes produced false alarms, increasing the risk of nuclear war, such as Soviet satellites in 1983 and Russian radar in 1995. After the dissolution of the Soviet Union in 1991 and the resultant end of the Cold War, the threat of a major nuclear war between the U.S. and Soviet Union has declined. Concern shifted to the prevention of localized nuclear conflicts resulting from nuclear proliferation, and the threat of nuclear terrorism. However, the threat of nuclear war is considered to have resurged since the start of the current phase of the Russo-Ukrainian war in 2022, particularly with regard to Russian threats to use nuclear weapons during the war.
Russ Prize "for automating DNA sequencing that revolutionized biomedicine and forensic science"; the 2011 National Medal of Science, presented at a White House ceremony by President Obama in early 2013; the IEEE Medal for Innovations in Healthcare Technology in 2014, and the 2016 Ellis Island Medal of Honor. In 2017 he received the NAS Award for Chemistry in Service to Society. In 2019 Hood was awarded the IRI Medal, established by the Industrial Research Institute (IRI).
It aids in normal mammary gland development. It is necessary for maintenance of the mammary bud cells. Loss of PTHrP or its receptor causes the mammary bud cells to change back into epidermal cells. In lactation, it may regulate the mobilization and transfer of calcium to the milk in conjunction with the calcium sensing receptors, as well as placental transfer of calcium.
Good Glue Sticks (French: La Colle universelle, literally "The Universal Glue") is a 1907 French short silent film by Georges Méliès. It was sold by Méliès's Star Film Company and is numbered 1005–1009 in its catalogues. Méliès plays the street peddler in the film, which uses substitution splices for its special effects. The earliest academic discussion of the film, in John Frazer's 1979 book Artificially Arranged Scenes: The Films of Georges Méliès, was based on a badly edited print, with the end of the film placed at the beginning. A 1981 guide to Méliès's films, published by the Centre national de la cinématographie, clarified the scene order.
Three major genes are involved in determination of Drosophila sex. These are sex-lethal, sisterless, and deadpan. Deadpan is an autosomal gene which inhibits sex-lethal, while sisterless is carried on the X chromosome and inhibits the action of deadpan. An AAX cell has twice as much deadpan as sisterless, so sex-lethal will be inhibited, creating a male. However, an AAXX cell will produce enough sisterless to inhibit the action of deadpan, allowing the sex-lethal gene to be transcribed to create a female. Later, control by deadpan and sisterless disappears and what becomes important is the form of the sex-lethal gene. A secondary promoter causes transcription in both males and females. Analysis of the cDNA has shown that different forms are expressed in males and females. Sex-lethal has been shown to affect the splicing of its own mRNA. In males, the third exon is included which encodes a stop codon, causing a truncated form to be produced. In the female version, the presence of sex-lethal causes this exon to be missed out; the other seven amino acids are produced as a full peptide chain, again giving a difference between males and females. Presence or absence of functional sex-lethal proteins now go on to affect the transcription of another protein known as doublesex. In the absence of sex-lethal, doublesex will have the fourth exon removed and be translated up to and including exon 6 (DSX-M[ale]), while in its presence the fourth exon which encodes a stop codon will produce a truncated version of the protein (DSX-F[emale]).
Sources: en.wikipedia.org
=== 1970s to 2011 === Though e-commerce on the dark web started around 2006, illicit goods were among the first items to be transacted using the internet, when in the early 1970s students at Stanford University and Massachusetts Institute of Technology used the ARPANET to coordinate the purchase of cannabis. By the end of the 1980s, newsgroups like alt.drugs would become online centres of drug discussion and information; however, any related deals were arranged entirely off-site directly between individuals. With the development and popularization of the World Wide Web and e-commerce in the 1990s, the tools to discuss or conduct illicit transactions became more widely available. One of the better-known web-based drug forums, The Hive, launched in 1997, serving as an information sharing forum for practical drug synthesis and legal discussion. The Hive was featured in a Dateline NBC special called The "X" Files in 2001, bringing the subject into public discourse. From 2003, the "Research Chemical Mailing List" (RCML) would discuss sourcing "Research Chemicals" from legal and grey sources as an alternative to forums such as alt.drugs.psychedelics. However Operation Web Tryp led to a series of website shut downs and arrests in this area. Since the year 2000, some of the emerging cyber-arms industry operates online, including the Eastern European "Cyber-arms Bazaar", trafficking in the most powerful crimeware and hacking tools. In the 2000s, early cybercrime and carding forums such as ShadowCrew experimented with drug wholesaling on a limited scale.
If two vertices have the same mass difference of one or several amino acids, a directed edge will be applied. The SeqMS algorithm, Lutefisk algorithm, Sherenga algorithm are some examples of this type.
==== Chain stores ==== Chain stores did not become popular in the United States until the end of World War I. It was reported in 1929 that chain stores accounted for 39% of all grocery sales in the United States. Chain stores' success is related to their ability to undersell smaller distributors. An anti-chain movement arose in response to the success of the chain stores during the Great Depression, but caused little detriment to the success and profitability of the chains.
Several scandals affected Uribe's administration; the Colombian parapolitics scandal expanded during his second term, involving numerous members of the administration's ruling coalition. Many pro-government lawmakers, such as the President's cousin Mario Uribe, were also investigated for their possible ties to paramilitary organizations. At the end of 2007, FARC agreed to release former senator Consuelo González, politician Clara Rojas, and her son Emmanuel, born in captivity after a relationship with one of her captors. Operation Emmanuel was proposed and set up by Venezuelan President Hugo Chávez, with the permission of the Colombian government. The mission was approved on December 26; however, on December 31, FARC claimed that the hostage release had been delayed because of Colombian military operations. At the same time, Colombian President Álvaro Uribe indicated that FARC had not freed the three hostages because Emmanuel may not be in their hands anymore. Two FARC gunmen were taken prisoner. Colombian authorities added that a boy matching Emmanuel's description had been taken to a hospital in San José del Guaviare in June 2005. The child was in poor condition; one of his arms was hurt, he had severe malnutrition, and he had diseases that are commonly suffered in the jungle. Having been evidently mistreated, the boy was later sent to a foster home in Bogotá, and DNA tests were announced to confirm his identity.
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 is a modified version of the natural hormone, with three amino acid changes and a fatty acid side chain added. These edits extend its half-life from minutes to about one week. The core receptor activity is retained.