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 2026-07-28 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.
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。
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。
| 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 |
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
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 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.
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.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L cells after food intake. The molecule is a 31-amino-acid backbone modified at three positions to resist cleavage by dipeptidyl peptidase-4, the enzyme that degrades native GLP-1 within minutes. A lysine residue at position 26 carries a linker and a C18 fatty diacid, which promotes binding to serum albumin and slows renal clearance. These changes extend the circulating half-life from roughly two minutes to about one week in humans.
The sequence incorporates alpha-aminoisobutyric acid at position 8, replacing the alanine found in the natural hormone. This substitution blocks the primary DPP-4 recognition site and contributes most of the enzymatic stability. Albumin binding further protects the peptide and reduces the frequency of administration required to maintain active plasma levels. Because the fatty acid chain increases lipophilicity, the compound is formulated as a solution rather than a simple aqueous buffer. Researchers describe the design as an incremental optimization of earlier GLP-1 analogs rather than a wholly new scaffold.
=== Chemistry === Pure lisinopril powder is white to off-white in color. Lisinopril is soluble in water (approximately 13 mg/L at room temperature), less soluble in methanol, and virtually insoluble in ethanol.
Brian Christian wrote that experts have pivoted "from the question of 'what they know' to the question of 'what they're doing with it'." Generative AI is often trained on unlicensed copyrighted works, including in domains such as images or computer code; the output is then used under the rationale of "fair use". Experts disagree about how well and under what circumstances this rationale will hold up in courts of law; relevant factors may include "the purpose and character of the use of the copyrighted work" and "the effect upon the potential market for the copyrighted work". Website owners can indicate that they do not want their content scraped via a "robots.txt" file. However, some companies will scrape content regardless because the robots.txt file has no real authority. In 2023, leading authors (including John Grisham and Jonathan Franzen) sued AI companies for using their work to train generative AI. Another discussed approach is to envision a separate sui generis system of protection for creations generated by AI to ensure fair attribution and compensation for human authors.
from the Pliocene strata of Mininco Formation (Chile), extending known distribution of capybaras west of the Andes. Selvatici et al. (2026) determine a previously unidentified mummified animal from the Homestake Gulch site (Yukon, Canada) as a late Holocene (approximately 3000-years-old) New World porcupine, report the recovery of the first complete ancient mitochondrial genome of a member of this species, and interpret this finding as evidence of appearance of the New World porcupines in the studied area after the appearance of the boreal forest in the aftermath of the Last Glacial Period. Carrillo et al. (2026) study the evolutionary history of caviomorph rodents on the basis of data from extant and extinct members of the group, providing evidence of different trajectories of taxonomic and morphological diversification of Chinchilloidea and Octodontoidea. Evidence from the study of tooth wear of caviomorph rodents from the Paleogene strata of the Shapaja in Peruvian Amazonia, indicative of diverse dietary strategies of the studied rodents, is presented by Robinet et al. (2026). Gutstein et al. (2026) describe fossil material of a member of the genus Cardiatherium from the Bahía Inglesa Formation (Chile), providing evidence of wetter environmental conditions in the area of present-day Pacific coast of the Atacama Desert during the late Miocene. Delinschi et al. (2026) confirm the validity of Sarmatosminthus gabuniai on the basis of the analysis of fossil material from Vallesian sites in Moldova, Romania and Ukraine.
== Further reading == Khan, Misbah H.; Victor, Frank; Rao, Babar; Sadick, Neil S. (2010). "Treatment of cellulite. Part I. Pathophysiology". Journal of the American Academy of Dermatology. 62 (3): 361–70, quiz 371–2. doi:10.1016/j.jaad.2009.10.042. PMID 20159304. Khan, Misbah H.; Victor, Frank; Rao, Babar; Sadick, Neil S. (2010). "Treatment of cellulite. Part II. Advances and controversies". Journal of the American Academy of Dermatology. 62 (3): 373–84, quiz 385–6. doi:10.1016/j.jaad.2009.10.041. PMID 20159305.
== Prediction == Because viscosity depends continuously on temperature and pressure, it cannot be fully characterized by a finite number of experimental measurements. Predictive formulas become necessary if experimental values are not available at the temperatures and pressures of interest. This capability is important for thermophysical simulations, in which the temperature and pressure of a fluid can vary continuously with space and time. A similar situation is encountered for mixtures of pure fluids, where the viscosity depends continuously on the concentration ratios of the constituent fluids For the simplest fluids, such as dilute monatomic gases and their mixtures, ab initio quantum mechanical computations can accurately predict viscosity in terms of fundamental atomic constants, i.e., without reference to existing viscosity measurements. For the special case of dilute helium, uncertainties in the ab initio calculated viscosity are two order of magnitudes smaller than uncertainties in experimental values. For slightly more complex fluids and mixtures at moderate densities (i.e. sub-critical densities) Revised Enskog Theory can be used to predict viscosities with some accuracy. Revised Enskog Theory is predictive in the sense that predictions for viscosity can be obtained using parameters fitted to other, pure-fluid thermodynamic properties or transport properties, thus requiring no a priori experimental viscosity measurements. For most fluids, high-accuracy, first-principles computations are not feasible.
Sources: en.wikipedia.org
In meteorites and in prebiotic experiments (e.g. Miller–Urey experiment) many more amino acids than the twenty standard amino acids are found, several of which are at higher concentrations than the standard ones. It has been conjectured that if amino acid based life were to arise elsewhere in the universe, no more than 75% of the amino acids would be in common. The most notable anomaly is the lack of aminobutyric acid.
==== Direct calculation when friction loss S is known ==== In typical engineering applications, there will be a set of given or known quantities. The acceleration of gravity g and the kinematic viscosity of the fluid ν are known, as are the diameter of the pipe D and its roughness height ε. If as well the head loss per unit length S is a known quantity, then the friction factor fD can be calculated directly from the chosen fitting function. Solving the Darcy–Weisbach equation for √fD,
New Brunswick was in turn split from Nova Scotia as part of a reorganization of Loyalist settlements in the Maritimes, which led to the incorporation of Saint John, New Brunswick, as Canada's first city. To accommodate the influx of English-speaking Loyalists in Central Canada, the Constitutional Act of 1791 divided the Province of Quebec into French-speaking Lower Canada (later Quebec) and English-speaking Upper Canada (later Ontario), granting each its own elected legislative assembly.
== Philanthropy == Kimmel was an important benefactor of New York University donating $10 million in 2005 and $15 million in 2006 to fund the Helen and Martin Kimmel Center for Stem Cell Biology, creating a professorship of molecular immunology, and contributing to the construction of the Helen and Martin Kimmel Center for University Life which houses the Skirball Center for the Performing Arts. Kimmel is also a significant contributor to the Weizmann Institute of Science in Rehovot, Israel funding the Helen and Martin Kimmel Institute for Magnetic Resonance, the Helen and Martin Kimmel Center for Molecular Design, the Helen and Martin Kimmel Hyperbaric & Advanced Wound Healing Center, and the Kimmel Center for Archaeological Science. Kimmel was a long time supporter of the Jewish Museum in New York City. Kimmel served as a trustee of New York University Langone Medical Center.
During an episode of Superstars, old friend Brian Pillman conducted an interview with Austin regarding his upcoming match. After Pillman inadvertently complimented Hart, Austin grew angry and attacked him. He then proceeded to wedge Pillman's ankle in between a steel chair and stomp on it, breaking his ankle in storyline. It would lead to the infamous "Pillman's got a gun" segment on Raw wherein Austin broke into Pillman's home while he was nursing his injury. At Survivor Series, Austin met Hart as expected in a match to determine the number-one contender for the WWF Championship, in what would be Austin's first major PPV match in his WWF career. Hart defeated Austin by using a turnbuckle to push himself backward while locked in the Million Dollar Dream, in a match that lasted almost half an hour. Despite the loss and his status as a heel character, Austin received significant cheers from the crowd. During the 1997 Royal Rumble match, Austin was originally eliminated by Hart but the officials did not see it; he snuck back into the ring and eliminated Hart by throwing him over the ropes, winning the match. This led to the first-ever PPV main event of Austin's WWF career at In Your House 13: Final Four, where he competed in a four corners elimination match against Hart, The Undertaker, and Vader for the vacant WWF Championship. Austin was eliminated early from the match after injuring his knee; Hart would win the match and the championship. Hart lost the championship the next night on Raw to Sycho Sid due to Austin's interference, continuing their feud.
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.
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。