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Last reviewed on 2025-09-04. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
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.
Receptor binding triggers G protein signaling that raises intracellular cyclic AMP in pancreatic beta cells. Insulin release follows in a glucose-dependent manner, so secretion increases when blood glucose is elevated and diminishes when it is not. The same signaling suppresses glucagon release from alpha cells and slows gastric emptying, which blunts the post-meal glucose rise. In the brain, receptor activation in regions such as the arcuate nucleus is associated with reduced appetite and lower energy intake. How much each of these effects contributes to overall weight change is not fully settled.
Two structural features account for the prolonged half-life of semaglutide. A modified amino acid at position 8 resists cleavage by dipeptidyl peptidase-4, the enzyme that rapidly degrades native GLP-1. A fatty diacid side chain binds serum albumin, which limits renal clearance and protects the peptide from enzymatic breakdown. These modifications yield a plasma half-life of approximately one week in humans, allowing once-weekly administration. The relationship between plasma concentration and clinical effect varies between individuals, and sources of that variability are still being characterized.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1 (GLP-1), a hormone released from intestinal L-cells after food intake. The compound belongs to the incretin mimetic class and acts at GLP-1 receptors distributed across pancreatic, gastrointestinal, cardiovascular, and central nervous system tissues. Compared with native GLP-1, the molecule carries structural changes that extend its activity from minutes to roughly one week. It is studied for glycemic control in type 2 diabetes and for weight management, and its effects on cardiovascular and other outcomes remain active research areas.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | free base, without counter-ion |
| Molecular weight | About 4114 Da | peptide backbone plus attached lipid chain |
| Plasma half-life | About 165 hours | supports once-weekly dosing in humans |
| Plasma protein binding | Greater than 99 percent | attributed mainly to serum albumin |
| Receptor target | GLP-1 receptor | Gs-coupled, raises intracellular cyclic AMP |
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.
Receptor activation raises intracellular cyclic AMP through Gs coupling, which promotes glucose-dependent insulin release and suppresses glucagon secretion when blood glucose is elevated. Effects outside the pancreas include slower gastric emptying and altered appetite signalling in the hypothalamus and hindbrain. The relative contribution of each tissue to overall metabolic outcomes remains an area of active investigation. Central mechanisms in particular are inferred mainly from animal models and indirect human measures rather than direct observation.
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 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.
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。
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。
=== For La Niña === 2000 Mozambique flood 2010 Pakistan floods 2010–2011 Queensland floods 2010–2012 La Niña event 2010–2011 Southern Africa floods 2010–2013 Southern United States and Mexico drought 2011 East Africa drought 2020 Atlantic hurricane season 2021 eastern Australia floods 2022 Suriname floods 2023 Auckland Anniversary Weekend floods 2020–2023 La Niña event
=== The 26Al – 26Mg chronometer === Another example of short-lived extinct radionuclide dating is the 26Al – 26Mg chronometer, which can be used to estimate the relative ages of chondrules. 26Al decays to 26Mg with a half-life of 720 000 years. The dating is simply a question of finding the deviation from the natural abundance of 26Mg (the product of 26Al decay) in comparison with the ratio of the stable isotopes 27Al/24Mg. The excess of 26Mg (often designated 26Mg*) is found by comparing the 26Mg/27Mg ratio to that of other Solar System materials. The 26Al – 26Mg chronometer gives an estimate of the time period for formation of primitive meteorites of only a few million years (1.4 million years for Chondrule formation).
== Clinical significance == A prolonged stimulation of these cells causes their hyperplasia. This is especially important in gastrinoma (the tumors in which there is an excessive secretion of gastrin), as this is one of the factors contributing to Zollinger–Ellison's syndrome. It was once believed that tumors of ECL origin form after a prolonged inhibition of gastric acid secretion, however there is no data to support this conclusion and proton pump inhibitors are not thought to contribute to gastric cancer.
=== Vince: The Roommate from Hell === First aired: 29 March 2009 Mayhem shows a tape of Josh and Adam, who are bullied by Josh's current and Adam's former roommate Vince, a basketball player. According to Adam, Vince doesn't pay rent, once threw him out of his own house, and broke his door. Vince accepts the challenge to fight, after initially hesitating. In addition to the money, Mayhem adds the additional stipulation that if Vince loses, he has to move out. He shows up to train at Mayhem's gym, during which he falls down after kicking Mayhem's bag, which causes Mayhem to laugh. He shows up to the fight and learns that his opponent will be former NFL wide receiver Michael Westbrook. During the first round, Vince tapped out four times in the first round, and was KO'd in the second round. He apologizes to Adam and Josh after the fight, but says in an interview afterwards that he will not be paying them the back rent, as the $9,000 they have just won will cover it. Adam notes that he will need a new roommate since Vince will be moving out, and asks Josh if he would like to move in with him, which Josh accepts.
Sources: en.wikipedia.org
== Clinical pharmacology == Benzhydrocodone is a prodrug of hydrocodone. Hydrocodone is a full agonist of the opioid receptors with a higher affinity for the mu-opioid receptor. Upon binding, hydrocodone produces an analgesic effect with no ceiling. The exact mechanism of analgesia is unknown. Acetaminophen is a non-opioid, non-salicylate analgesic. The specific mechanism of analgesia has not been determined.
Calcitonin gene-related peptide 2 (CGRP2), also called calcitonin related polypeptide beta, is a hormone that in humans is encoded by the CALCB gene (previously CALC2). Like the related hormone, calcitonin gene-related peptide 1 (CGRP1), this hormone induces vasodilation (relaxation of blood vessels) through the activation of the CGRP receptor. This form of calcitonin gene-related peptide is traditionally considered to be the primary form used in the enteric nervous system (nervous system in the gut). The gene that encodes CGRP1, CALCA, also encodes the blood-calcium-reducing hormone calcitonin, but despite its name, this protein is encoded by a distinct gene (CALCB). This hormone activates the CGRP receptor, which is a two protein (heterodimer) complex that is composed of RAMP1 and CALCRL.
== Society and culture == Chlordiazepoxide is the drug referenced in the Netflix series "The Queen's Gambit," under the commercial name Librium. It also appears prominently in the HBO series "The Pitt." In “Infinite Jest”, by David Foster Wallace, a nurse “negotiated a trade of shoes for Librium” with the character Tiny Ewell. In the first episode of Yes, Minister, Jim Hacker tells his wife Annie to take a Librium when she couldn't find a cigarette.
Sources: en.wikipedia.org
The College of Pharmacy is one of the oldest in the United States, and the oldest west of the Allegheny Mountains. It offers PharmD, MS and PhD degrees, including some online programs. Its graduates have a 100% placement rate prior to graduation. It is ranked in the top 25% of pharmacy programs in the US.
In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate. The combination of glucose from noncarbohydrates origin, such as fat and proteins. This only happens when glycogen supplies in the liver are worn out. The pathway is a crucial reversal of glycolysis from pyruvate to glucose and can use many sources like amino acids, glycerol and Krebs Cycle. Large scale protein and fat catabolism usually occur when those suffer from starvation or certain endocrine disorders. The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides. The combined pathways of glycolysis during exercise, lactate's crossing via the bloodstream to the liver, subsequent gluconeogenesis and release of glucose into the bloodstream is called the Cori cycle.
Oxycodone, like other opioid analgesics, tends to induce feelings of euphoria, relaxation, and reduced anxiety in those who are occasional users. The abuse of oxycodone, as well as related opioids more broadly, is not unique to the United States and it is a common drug of abuse globally.
== History == Daptomycin, originally designated as LY 146032, was discovered by researchers at Eli Lilly and Company in the late 1980s from the actinomycete Streptomyces roseosporus. LY 146032 showed promise in phase I/II clinical trials for treatment of infection caused by Gram-positive organisms. Lilly ceased development because high-dose therapy was associated with adverse effects on skeletal muscle, including myalgia. The rights to LY 146032 were acquired by Cubist Pharmaceuticals in 1997, which following U.S. Food and Drug Administration (FDA) approval in September 2003, for use in people older than 18 years, began marketing the drug under the trade name Cubicin. Cubicin is marketed in the EU and in several other countries by Novartis following its purchase of Chiron Corporation, the previous licensee. In July 2016 the FDA approved a reformulated version of daptomycin, designated Cubicin RF, which is stored at controlled room temperature rather than requiring refrigeration. In December 2014, Merck & Co. reached an agreement to acquire Cubist Pharmaceuticals for a total transaction value of approximately $9.5 billion, comprising an equity valuation of $8.4 billion at $102 per share in cash and $1.1 billion in assumed net debt, with the transaction expected to close in the first quarter of 2015.
Sources: en.wikipedia.org
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.
Albumin is the most abundant protein in plasma and carries molecules that bear fatty-acid chains. Binding shields the peptide from renal filtration and from peptidases, keeping a circulating reservoir. Slow release from this reservoir produces sustained receptor occupancy and supports infrequent dosing.
The insulinotropic effect is glucose-dependent, meaning secretion increases mainly when glucose is elevated. This property is often described as lowering the chance of hypoglycaemia when the compound is used alone. Other glucose-lowering agents used at the same time can still cause low blood glucose.
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and cleared quickly. Semaglutide carries a position 8 substitution that blocks that cleavage and a fatty diacid chain that binds albumin. Together these changes extend its circulating half-life to about one week.