The short version of receptor agonist fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-12-23. Anything still debated is marked as such rather than presented as settled.
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.
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.
| 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 |
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。
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.
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.
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.
== Climate change == Climate change exacerbates threats to aquatic plants through rising temperatures, altered precipitation patterns, and increased frequency of extreme weather events. Warmer temperatures can favor invasive species that outcompete native plants. For example, studies predict that the ranges of invasive species like Egeria densa and Myriophyllum aquaticum may expand significantly by 2070 due to climate change. Additionally, earlier spring warming allows invasive species to establish before native plants, giving them a competitive advantage. Climate-induced changes also affect water levels and flow regimes, impacting aquatic plant distribution and health. Droughts can reduce water availability, while intense storms can lead to increased runoff and sedimentation, both detrimental to aquatic vegetation.
Aprataxin is 342 amino acids long and consists of FHA domain and HIT-ZnF catalyc core. It works by binding to adenylated DNA and removing AMP by catalytic side. Aprataxin is localised in the nucleus and mitochondria, which means aprataxin participates in mitochondrial DNA repair. This protein participates in base excision repair (BER) by returning abortive DNA ligation into scheduled repair by DNA polymerase beta, which would remove 5'-deoxyribosephosphate residue (dRP) and fill the gap; consequently, DNA ligase III-XRCC1 complex would seal the gap; consequently this mechanism is hampered in AOA1. Also, it might participate in microhomology-mediated end joining (MMEJ) by associating with XRCC1 and DNA ligase III and safeguarding DNA from abortive ligations by DNA ligase I, which might, again, be hampered in AOA1. iPSC with AOA1-associated mutation showed hindered differentiation into neurons which could be responsinble for early onset. Additionally, these neurons showed increased levels of cleaved PARP1 and decreased levels of APEX1. Due to the unique structure of chromatin in Purkinje cells, DNA damage (caused by aprataxin dysfunction) would hamper RNA polymerase II function, which would lead to improper splicing of some genes (such as: ITPR1, GRID2, CA8) and consequeent formation of R-loops; R-loops can exacerbate DNA damage. Because of dysregulation of genes, this would lead to ataxia. Decreased levels of albumin and elevated alpha-fetoprotein in AOA1 might be caused by transcriptional dysregulation in the liver.
He added that efforts were ongoing to secure and defend remote and hard-to-reach areas. Also, on 25 March, two TTP militants were killed in a CTD operation in Tank District. On 27 March, BBC Dari citing satellite imagery, reported that Pakistan had fenced off 32 square kilometers of land in Paktika province, raising speculation that it may have occupied the area. According to BBC Dari, no visible fence line could be seen on 20 March, but by 23 March satellite imagery showed a new fence that had been built 12 kilometers inside Afghan territory. BBC Dari also reported that, after the completion of the first fence line, a second fence was built at the mouth of the same area, more than 13.5 kilometers inside Afghan territory. However, the Afghan Ministry of Defense said that Mali Khan Siddiq, the deputy army chief of the Afghan armed forces, had visited border areas in Paktika and dismissed claims that Pakistani forces had occupied Terwa district as false propaganda. Naseer Ahmad Faiq, Afghanistan's acting Permanent Representative to the UN, said that if reports of Pakistan seizing Afghan territory were true, they would amount to "naked aggression" and should be condemned in the strongest terms. He added that any occupation of Afghan land would be illegal under international law, violate the UN Charter and Afghanistan's territorial integrity, and that Afghanistan's sovereignty was non-negotiable.
== Neuron-intrinsic changes == Immediately following injury, neurons undergo a large number of transcriptional and proteomic changes which switch the cell from a mature, synaptically active neuron to a synaptically silent, growth state. This process is dependent on new transcription, as blocking the ability of cells to transcribe new mRNA severely impairs regeneration. A number of signaling pathways have been shown to be turned on by axon injury and help to enable long distance regeneration including BMP, TGFβ, and MAPKs. Similarly, a growing number of transcription factors also boost the regenerative capacity of peripheral neurons including ASCL1, ATF3, CREB1, HIF1α, JUN, KLF6, KLF7, MYC, SMAD1, SMAD2, SMAD3, SOX11, SRF, STAT3, TP53, and XBP1. Several of these can also boost the regenerative capacity of CNS neurons, making them potential therapeutic targets for treating spinal cord injury and stroke.
=== Naturally occurring inhibitors === The plant alkaloid berberine inhibits the transcription of the PCSK9 gene in immortalized human hepatocytes in vitro, and lowers serum PCSK9 in mice and hamsters in vivo. It has been speculated that this action contributes to the ability of berberine to lower serum cholesterol. Annexin A2, an endogenous protein, is a natural inhibitor of PCSK9 activity.
Sources: en.wikipedia.org
The city currently has a large number of rail and road work sites. Although this activity has increased as a result of the 2006 Winter Olympics, parts of it had long been planned. Some of the work sites deal with general roadworks to improve traffic flow, such as underpasses and flyovers, but two projects are of major importance and will radically change the shape of the city. One is the Spina Centrale ('Central Spine') project which includes the doubling of a major railway crossing the city, the Turin-Milan railway locally known as Passante Ferroviario di Torino ('Turin Railway Bypass'). The railroad previously ran in a trench, which will now be covered by a major boulevard running from north to south of Turin, in a central position along the city. Porta Susa, on this section, will become Turin's main station to substitute the terminus of Porta Nuova with a through station. Other important stations are Stura, Rebaudengo, Lingotto and Madonna di Campagna railway stations, though not all of them belong to the layout of the Spina Centrale.
DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.
In the Netherlands, Cyber Defense is nationally coordinated by the National Cyber Security Centre (NCSC). The Dutch Ministry of Defense laid out a cyber strategy in 2011. The first focus was to improve the cyber defense handled by the Joint IT command (JIVC). To improve intel operations, the intel community in the Netherlands (including the military intel organization, MIVD) has set up the Joint Sigint Cyber Unit (JSCU). The Ministry of Defense oversees an offensive cyber force, called the Defense Cyber Command (DCC).
In contrast to other mechanical disruption methods the Microfluidizer breaks the cell membranes efficiently but gently, resulting in relatively large cell wall fragments (450 nm), and thus making it easier to separate the cell contents. This can lead to shorter filtration times and better centrifugation separation. Microfluidizer technology scales from one milliliter to thousands of liters.
DMT derived from plant-based sources has been used as an entheogen in South America for thousands of years. DMT was first synthesized in 1931 by Canadian chemist Richard Manske. In general, its discovery as a natural product is credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima, who isolated an alkaloid he named nigerina (nigerine) from the root bark of Mimosa tenuiflora in 1946. However, in a careful review of the case Jonathan Ott shows that the empirical formula for nigerine determined by Gonçalves de Lima, which notably contains an atom of oxygen, can match only a partial, "impure" or "contaminated" form of DMT. It was only in 1959, when Gonçalves de Lima provided American chemists a sample of Mimosa tenuiflora roots, that DMT was unequivocally identified in this plant material. Less ambiguous is the case of isolation and formal identification of DMT in 1955 in seeds and pods of Anadenanthera peregrina by a team of American chemists led by Evan Horning (1916-1993). Since 1955, DMT has been found in a number of organisms: in at least fifty plant species belonging to ten families, and in at least four animal species, including one gorgonian and three mammalian species (including humans). In terms of a scientific understanding, the hallucinogenic effects of DMT were not uncovered until 1956 by Hungarian chemist and psychiatrist Stephen Szára.
Sources: en.wikipedia.org
In cancerous cells, initiation factors assist in cellular transformation and development of tumors. The survival and growth of cancer is directly related to the modification of initiation factors and is used as a target for pharmaceuticals. Cells need increased energy when cancerous and derive this energy from proteins. Over-expression of initiation factors correlates with cancers, as they increase protein synthesis for proteins needed in cancers. Some initiation factors, such as eIF4E, are important in synthesizing specific proteins needed for the proliferation and survival of cancer. The careful selection of proteins ensures that proteins that are usually limited in translation and only proteins needed for cancer cell growth will be synthesized. This includes proteins involved in growth, malignancy, and angiogenesis. The eIF4E factor, along with eIF4A and eIF4G, also play a role in transitioning benign cancer cells to metastatic. The largest initiation factor, eIF3, is another significant initiation factor in human cancers. Due to its role in creating the 43S pre-initiation complex, it helps to bind the ribosomal subunit to the mRNA. The initiation factor has been linked to cancers through over-expression. For example, one of the thirteen eIF3 proteins, eIF3c, interacts with and represses proteins used in tumor suppression. Limited expression of certain eIF3 proteins, such as eIF3a an eIF3d, has been proven to decrease the vigorous growth of cancer cells. The over-expression of eIF3a has been linked to breast, lung, cervix, esophagus, stomach, and colon cancers.
== Antibody elution == Antibody elution is the process of removing antibodies that are attached to their targets, such as the surface of red blood cells. Techniques include using heat, a freeze-thaw cycle, ultrasound, acids, or organic solvents.
In this case a second brand is added at the top of their left rear leg, the croup. The second brand aids in identifying a particular horse among the hundreds or thousands under care. This mark uses Arabic numerals 4 inches (10 cm) high and displays the horse's tag number. If a horse has undergone special medical treatment the hip brand is preceded by a letter code. A hip brand preceded by "LB" for example indicates that a mare was treated with fertility control by BLM before being released back onto the range.
Newsom declared a state of emergency on March 4, 2020, after the first death in California attributable to the novel SARS-CoV-2 coronavirus disease (COVID-19). His stated intention was to help California prepare for and contain COVID-19's spread. The emergency declaration allowed state agencies to more easily procure equipment and services, share information on patients and alleviated restrictions on the use of state-owned properties and facilities. Newsom also announced that mitigation policies for the state's estimated 108,000 unsheltered homeless people would be prioritized, with a significant push to move them indoors. Newsom issued an executive order that allowed the state to commandeer hotels and medical facilities to treat COVID-19 patients and permitted government officials to hold teleconferences in private without violating open meeting laws. He also directed local school districts to make their own decisions on school closures, but used an executive order to ensure students' needs would be met whether or not their school was physically open. The U.S. Department of Agriculture approved the Newsom administration's request to offer meal service during school closures, which included families being able to pick up those meals at libraries, parks, or other off-campus locations. Roughly 80% of students at California's public schools receive free or reduced-price meals. This executive order included continued funding for remote learning opportunities and child care options during workday hours.
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.
Reverse-phase high-performance liquid chromatography with ultraviolet detection is the usual choice, with results reported as area percent. Complementary methods such as size-exclusion chromatography and mass spectrometry are needed because a single separation cannot resolve every impurity class. Purity figures are therefore method dependent and should always be read alongside the technique used.