Everything below concerns reference standard. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-07-29. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
Identity and purity are assessed with reversed-phase high-performance liquid chromatography, which separates the peptide from related impurities by hydrophobicity. Mass spectrometry confirms molecular weight and detects truncation or modification products. Peptide mapping after enzymatic digestion verifies the amino acid sequence. Quantitation is often performed by LC-MS/MS or by immunoassay, and the two approaches can give different values because they measure different things. Method validation parameters such as accuracy, precision, and limit of quantitation are reported alongside results.
Certificate of analysis documents from suppliers typically report purity by chromatographic area, water content, and counter-ion identity. Independent verification is advisable because reported values can be generated under differing conditions. Impurity profiles matter for research use, where aggregates, deamidation products, and residual solvents may influence experimental results. Container, lot, and chain-of-custody records support traceability. Analytical results are method-dependent, so comparisons between laboratories require the same procedure and reference standards.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | Parent peptide; salt forms also reported |
| Molecular mass | about 4113.6 Da | Average mass of the free peptide |
| Peptide length | 31 amino acids | Backbone related to GLP-1(7-37) |
| Key substitution | Aib at position 8 | Blocks DPP-4 cleavage |
| Albumin binding | Via C-18 diacid side chain | Prolongs circulation time |
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.
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
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。
Degradation proceeds along several parallel routes. Deamidation of asparagine and glutamine residues generates charged variants that shift retention time in chromatographic analysis. Oxidation targets methionine and can be accelerated by trace metals or dissolved oxygen. Non-covalent aggregation produces dimers, oligomers, and larger species that are difficult to reverse. Isomerisation at aspartate residues is slower but measurable under thermal stress. The distribution among these pathways depends on pH, buffer composition, ionic strength, and the presence of excipients such as sugars or surfactants.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 nm is the standard purity method, reported as area percent. Mass spectrometry, usually with electrospray ionisation, confirms identity and reveals covalent modifications. Size-exclusion chromatography quantifies aggregates and fragments. Peptide mapping after enzymatic digestion localises changes to specific sequence regions. Circular dichroism and infrared spectroscopy report on secondary structure, while light scattering tracks particle formation in liquid formulations. No single technique captures every quality attribute.
==== Other pain ==== Paracetamol fails to relieve procedural pain in newborn babies. For perineal pain postpartum paracetamol appears to be less effective than nonsteroidal anti-inflammatory drugs (NSAIDs). The studies to support or refute the use of paracetamol for cancer pain and neuropathic pain are lacking. There is limited evidence in favor of the use of the intravenous form of paracetamol for acute pain control in the emergency department. The combination of paracetamol with caffeine is superior to paracetamol alone for the treatment of acute pain.
The Twin Towers, Marriott World Trade Center (3 WTC), 7 WTC, and St. Nicholas Greek Orthodox Church were destroyed. The U.S. Customs House (6 World Trade Center), 4 World Trade Center, 5 World Trade Center, and both pedestrian bridges connecting buildings were severely damaged. All surrounding streets were in ruins. The last fires at the World Trade Center site were extinguished on December 20. The Deutsche Bank Building was damaged and was later condemned as uninhabitable because of toxic conditions; it was deconstructed starting in 2007. Buildings of the World Financial Center were damaged. The Borough of Manhattan Community College's Fiterman Hall was condemned due to extensive damage, and then reopened in 2012. Other neighboring buildings (including 90 West Street and the Verizon Building) suffered major damage but have been restored. World Financial Center buildings, One Liberty Plaza, the Millennium Hilton, and 90 Church Street had moderate damage and have been restored. Communications equipment on top of the North Tower was also destroyed, with only WCBS-TV maintaining a backup transmitter on the Empire State Building, but media stations were quickly able to reroute the signals and resume their broadcasts. The PATH train system's World Trade Center station was located under the complex and was demolished when the towers collapsed. The tunnels leading to Exchange Place station in Jersey City were flooded with water. The station was rebuilt as the $4 billion World Trade Center Transportation Hub, which reopened in March 2015.
==== Agrochemicals ==== Agrochemical companies are the second largest users of fine chemicals. Most products have a "pharmaceutical heritage". As a consequence of an intensive M&A activity (Mergers and Acquisitions) over the past 10–20 years, the industry now is more consolidated than the pharmaceutical industry. The top 10 companies, led by Syngenta, Switzerland; Bayer Cropsciences, Germany: Monsanto, USA; BASF Crop Protection, Germany, and Dow Agrosciences, USA have a share of almost 95% of the total 2,000,000 tons / $48.5 billion pesticide output in 2010. Since the 1990s, the R&D effort has been focused mainly on gene modified (GM) seeds. At both Monsanto and DuPont's seed subsidiary, Pioneer Hi-Bred, the GM seed businesses already account for more than 50% of total sales. 100 new LMW agrochemicals were launched between 2000–2009. However, only 8 products achieved sales in excess of $100 million per year. Generics play a bigger role in the agro than in the pharma industry. They represent some 70% of the global market. China National Chemical Corp is the world's largest supplier of generic farm chemicals. Mahkteshim Agan, Israel, and Cheminova, Denmark, rank second and third. Apart from these multibillion-dollar companies, there are hundreds of smaller firms with sales of less than $50 million per year, mainly in India and China. The incidence of the cost of the active ingredient is about 33%, much higher than in drugs.
It is generally considered less sedating and causes less tolerance than traditional 1,4-benzodiazepines, partially because it binds less to subunits that cause sedation. N-desmethylclobazam, is the active metabolite of the benzodiazepine, clobazam. It works by enhancing GABA-activated chloride influx at GABAA receptor, creating a hyperpolarizing, inhibitory postsynaptic potential. The primary active metabolite N-desmethylclobazam, circulates at higher levels than the parent drug at therapeutic dosages. Plasma concentrations of N-desmethylclobazam are approximately 3–5 times higher than those of clobazam. The primary active metabolite of clobazam, is crucial for its prolonged anti-anxiety and anti-epileptic effects, acting similarly on GABAA receptors but with potentially greater importance in long-term therapy, especially for epilepsy, and is largely responsible for the drug's overall clinical action. It was also reported that these effects were inhibited by the GABA antagonist flumazenil, and that clobazam acts more efficiently in GABA-deficient brain tissue.
Sources: en.wikipedia.org
=== Controversy === Use of this class of drugs has a history of criticism in residential care. As the drugs used can make patients calmer and more compliant, critics claim that the drugs can be overused. Outside doctors can feel under pressure from care home staff. In an official review commissioned by UK government ministers it was reported that the needless use of antipsychotic medication in dementia care was widespread and was linked to 1800 deaths per year. In the US, the government has initiated legal action against the pharmaceutical company Johnson & Johnson for allegedly paying kickbacks to Omnicare to promote its antipsychotic risperidone (Risperdal) in nursing homes. There has also been controversy about the role of pharmaceutical companies in marketing and promoting antipsychotics, including allegations of downplaying or covering up adverse effects, expanding the number of conditions or illegally promoting off-label usage; influencing drug trials (or their publication) to try to show that the expensive and profitable newer atypicals were superior to the older cheaper typicals that were out of patent. Following charges of illegal marketing, settlements by two large pharmaceutical companies in the US set records for the largest criminal fines ever imposed on corporations. One case involved Eli Lilly and Company's antipsychotic Zyprexa, and the other involved Bextra. In the Bextra case, the government also charged Pfizer with illegally marketing another antipsychotic, Geodon.
== History and literature == The compound was discovered by Justus von Liebig and Friedrich Wöhler. It is one of the oldest named organic compounds. It was originally prepared in 1818 by Luigi Valentino Brugnatelli (1761-1818) and was named in 1838 by Wöhler and Liebig. The name "Alloxan" emerged from an amalgamation of the words "Allantoïn" and "Oxalsäure" (oxalic acid). The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan, and McLetchie in 1943. The name is derived from allantoin, a product of uric acid excreted by the fetus into the allantois, and oxaluric acid derived from oxalic acid and urea, found in urine. Alloxan was used in the production of the purple dye murexide, discovered by Carl Wilhelm Scheele in 1776. Murexide is the product of the complex in-situ multistep reaction of alloxantin and gaseous ammonia. Murexide results from the condensation of the unisolated intermediate uramil with alloxan liberated during the course of the reaction.
In 1989, President Bush ordered the invasion of Panama to depose the country's de facto dictator, Manuel Noriega. The invasion was condemned by the United Nations General Assembly as a "flagrant violation of international law". The US later provided intelligence about flights with civilians suspected of carrying drugs to Colombian and Peruvian officials; after several planes were shot down, the Clinton administration ceased its assistance in providing information. According to the United States Navy, the United States Coast Guard regularly works with the Navy to intercept ships believed to be used for drug smuggling operations. The United States Armed Forces broadly engage in joint anti-drug training exercises with other countries, including Colombia and Mexico. During the presidency of George W. Bush, the AUMF Act and the Specially Designated Global Terrorist designation in the context of the war on terror laid the groundwork for subsequent classifications. President of Venezuela Nicolás Maduro was originally indicted in the US on drug charges including narcoterrorism in 2020.
Sources: en.wikipedia.org
Health Canada followed with similar label updates in 2021, and Australia's Therapeutic Goods Administration aligned all SSRI and SNRI product information in 2024, noting that venlafaxine already carried a warning about persistent sexual dysfunction.
One dose is about 93% effective while two doses of the vaccine are about 97% effective at preventing measles. Before the widespread use of the vaccine, measles was so common that infection was considered "as inevitable as death and taxes." In the United States, reported cases of measles fell from 3 to 4 million with 400 to 500 deaths to tens of thousands of cases per year following introduction of two measles vaccines in 1963 (both an inactivated and a live attenuated vaccine (Edmonston B strain) were licensed for use, see chart at right). Increasing uptake of the vaccine following outbreaks in 1971 and 1977 brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. No more than 220 cases were reported in any year from 1997 to 2013, and the disease was believed no longer endemic in the United States. In 2014, 667 cases were reported. The benefits of measles vaccination in preventing illness, disability, and death have been well documented. Within the first 20 years of being licensed in the U.S., measles vaccination prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability, and 5,200 deaths. From 1999 to 2004 a strategy led by the WHO and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. The vaccine for measles led to the near-complete elimination of the disease in the United States and other developed countries.
Mechanism The reaction of tetrazines with trans-cyclooctenes is a highly specific biorthogonal reaction recognized for its rapid reaction rates, compatibility with physiological environments, and its metal-free characteristics. Commonly referred to as tetrazine ligation, the reaction was initially reported in 2008 and has since become a widely adopted bioorthogonal chemistry tool in both in vivo and in vitro studies. The tetrazine ligation is a specific type of inverse electron demand Diels-Alder (shown in the second mechanism in Figure 13) (iEDDA) [4+2] cycloaddition. The mechanism involves an electron-deficient tetrazine, typically a substituted 3,6-diaryl-s-tetrazine functioning as the diene and an electron-rich strained alkene, typically a trans-cyclooctene (TCO) compound, serving as the dienophile (shown in Figure 14). Trans-cyclooctenes have a high strain energy of 17.9 kcal/mol due to their non-planar double bond, making it very reactive and a strong dienophile. Following the initial iEDDA, a retro-Diels-Alder (shown in the last mechanism in Figure 13) reaction occurs, resulting in the expulsion of nitrogen gas (N2), driving the reaction forward. This promotes the irreversible nature of the reaction, which enhances its suitability for bio-labeling applications. This reaction has fast reactivity at low concentrations, with second order rate constants ranging from 1–106 M−1 s−1 depending on the specific tetrazine and TCO pair.
Sources: en.wikipedia.org
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.
The side chain enables reversible binding to albumin in the bloodstream, which protects the peptide from rapid renal clearance. This extends the interval between administrations compared with unmodified GLP-1.
No. It shares much of the native sequence but carries substitutions and an added side chain. These changes increase stability against enzymatic breakdown.
The lyophilized powder is dissolved in a suitable solvent, often sterile water or a buffered diluent, with gentle mixing rather than vigorous shaking. Foaming and shear should be avoided because they can promote aggregation. The resulting solution is then stored cold and protected from light.