The short version of albumin binding fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-07-17 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.
容器与密封系统同样参与稳定性表现。硅油涂层、胶塞材质与顶空氧含量可能改变聚集速率与氧化水平。分析结果因此需要在完整包装形式下评估，而不能仅凭原料药数据推断。法规文件通常要求同时提交批次数据与代表性容器中的稳定性趋势。
关于降解产物的免疫原性风险，文献中仍有讨论空间。体外聚集水平与临床免疫反应之间的定量关系尚未确立。多数公开研究只报告理化指标，缺少长期随访的对应数据。这一问题在生物类似物比对中尤其受到关注。
市售注射用制剂通常要求在二至八摄氏度冷藏保存，并避免光照与冻结。部分多剂量笔在首次使用后允许在不超过三十摄氏度的环境中存放有限周数，具体期限由辅料与防腐剂体系决定。反复冻融会促进肽链聚集并改变可见颗粒计数，因此应予避免。冻干粉末在干燥、避光、低温条件下更为稳定。溶液配制后宜使用低吸附容器，以减少肽类在塑料或玻璃表面的损失。
| 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 |
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.
Reported molecular weight is approximately 4113.6 daltons for the free base, and the peptide is supplied as a lyophilized powder or in buffered liquid form depending on the intended use. It is freely soluble in water when formulated with appropriate excipients, though the unconjugated peptide shows limited stability at neutral pH over long periods. Analytical characterization typically relies on reversed-phase high-performance liquid chromatography and mass spectrometry. Purity specifications for research-grade material commonly exceed ninety-five percent by area. Isotopic and impurity profiles differ between suppliers.
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.
Lyophilised semaglutide is generally held at -20 °C or below, protected from light and moisture. Reconstituted solutions are typically kept at 2-8 °C and used within a defined window because degradation accumulates over time. Repeated freeze-thaw cycles are discouraged, since each cycle can promote aggregation and reduce monomeric content. Room-temperature stability of the solid has been examined in some studies but remains incompletely characterised for long durations, so cold storage is the conservative default for research material.
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.
=== 2009 Tongchuan, Shaanxi, China === In 2009, a Chinese cement company in Tongchuan, Shaanxi Province was demolishing an old, unused cement plant and did not follow standards for handling radioactive materials. This caused some caesium-137 from a measuring instrument to be included with eight truckloads of scrap metal on its way to a steel mill, where the radioactive caesium was melted down into the steel.
The efficacy of lowering HbA1c in the gemigliptin group was generally consistent across the subgroups based on age (<65 or ≥65 years), gender, duration of T2DM (5, >5 to 10, or >10 years), and baseline body mass index (BMI, <25 or ≥25 kg/m2). In addition, gemigliptin groups led to a significantly greater inhibition of plasma DPP-4 compared to sitagliptin. This study was extended by 28 weeks in order to evaluate the long-term efficacy and safety of gemigliptin. All treatment groups showed clinically and statistically (P<0.0001) significant improvement in glycemic control from baseline after 52 weeks. The reduction from the baseline in HbA1c was –1.06 (95% CI, –1.28 to –0.85) in the patients who continued to receive gemigliptin 50 mg qd. Add-on to metformin and glimepiride In this multicenter, randomized, blinded, phase III study (study identifier: LG-DPCL010, TROICA study; ClinicalTrials.gov registration number: NCT01990469), eligible patients with inadequate glycemic control (7%≤HbA1c≤11%) were randomized to gemigliptin 50 mg qd (n=109) or placebo (n= 110). The baseline demographics were similar between groups (age, 60.9 years; BMI, 24.9 kg/m2; duration of T2DM, 12.9 years), with mean±standard deviation (SD) baseline HbA1c of 8.12%± 0.82% in the gemigliptin group and 8.15%±0.89% in the placebo group. At week 24, the adjusted mean±standard error change for HbA1c with gemigliptin was –0.88%±0.17% (change with placebo –0.01%±0.18%; difference –0.87%±0.12%; 95% CI, –1.09 to –0.64; P<0.0001).
Sulfuric acid is rarely encountered naturally on Earth in anhydrous form, due to its great affinity for water. Dilute sulfuric acid is a constituent of acid rain, which is formed by atmospheric oxidation of sulfur dioxide in the presence of water—i.e. oxidation of sulfurous acid. When sulfur-containing fuels such as coal or oil are burned, sulfur dioxide is the main byproduct (besides the chief products carbon oxides and water). Sulfuric acid is formed naturally by the oxidation of sulfide minerals, such as pyrite:
Sources: en.wikipedia.org
== Genetics == Biallelic pathogenic variants in GAMT are associated with guanidinoacetate methyltransferase deficiency. Over 70 variants have been reported in the GAMT gene. This gene codes for the enzyme guanidinoacetate methyltransferase (GAMT), which participates in the two-step synthesis of the compound creatine from amino acids glycine, arginine and methionine. Specifically, GAMT controls the second step of the sequence, in which creatine is produced from another compound called guanidinoacetate. GAA is toxic, and because GAMT patients lack the enzyme used to convert GAA to creatine, a build-up of GAA occurs in the brain and other tissues. This accumulation of GAA is thought to cause the more severe symptoms of GATM deficiency. The effects of GAMT deficiency are most severe in organs and tissues that require large amounts of energy, such as the brain and muscles. This disorder is inherited in an autosomal recessive manner, which means the causative gene is located on an autosome, and two defective copies of the gene – one from each parent – are required to inherit the disorder. The parents both carry one pathogenic variant; however, they are not affected by the disorder. As carriers, the residual activity of approximately 50% is enough to avoid clinical complications. Any siblings of an GAMT deficient individual have a 25% chance of also being GAMT deficient, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Investors at several venture capital firms, including executives at Peter Thiel's Founders Fund, Union Square Ventures and Coatue Management urged their portfolio companies to withdraw their deposits from the bank, with Founders Fund withdrawing all of its funds from the bank by the morning of March 9. By the close of business that day, customers had withdrawn $42 billion, leaving the bank with a negative cash balance of about $958 million. Among the financial services companies receiving money from SVB customers were Brex, JPMorgan Chase, Morgan Stanley and First Republic Bank. The value of SVB's shares plummeted until a trading halt was implemented on the morning of March 10. On February 27, SVB Financial Group CEO Greg Becker sold 12,451 shares of company stock, worth $3.6 million, through an executive trading plan that he filed with the SEC under Rule 10b5-1 on January 26. The rule has been criticized as a loophole allowing for insider trading. Beginning April 1, the SEC will require a minimum 90-day cooling period for most executive trading plans.
== Indications (biomarkers) == The most common biomarker for exposure to AzM is the inhibition of AChE. Also other esterase enzymes as CaE and BChE are inhibited by AzM. In general AzM exposure can be better detected by AChE inhibition than CaE inhibition. In amphibians and also zebrafish, AChE is a more sensitive biomarker for low AzM exposure-levels. As already mentioned in paragraph 7 “detoxification”, AzM can be metabolized into nontoxic dimethylated alkylphosphates (AP), with the help of CYP450 and glutathione. These APs are: dimethylphosphate (DM), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP). These three metabolites may be excreted into the urine and can be used as reliable biomarkers of exposure to AzM. However these metabolites are not specific to AzM, because other organophosphate pesticides might also be metabolized into the three alkylphosphates. The amount of erythrocyte acetylcholinesterase (RBE-AChE) in the blood can also be used as a biomarker of effect for AzM. According to Zavon (1965) RBC-AChE is the best indicator of AChE activity at the nerve synapse, because this closely parallels the level of AChE in the CNS and PNS. A depression of RBC-AChE will correlate with effects due to a rapid depression of AChE enzymes found in other tissues, this is due to the fact that both enzymes can be inhibited by AzM.
=== Sources === Philippe Jaussaud; Édouard-Raoul Brygoo (2004). Du Jardin au Muséum. Archives (in French). Paris: Muséum national d'histoire naturelle. p. 630. ISBN 978-2-85653-565-3. Annuaire et sites du Muséum national d'histoire naturelle, 40 p., MNHN, Paris, rééditions décennales. Ghislaine Prévos, Service documentation du Département des Galeries du Muséum national d'histoire naturelle, annuaire biographique du personnel.
Sources: en.wikipedia.org
Caesium-134 is found in spent nuclear fuel but is not produced by nuclear weapon explosions, as it is only formed by neutron capture on stable Cs-133, which is only produced by beta decay of Xe-133 with a half-life of 3 days. Cs-134 has a half-life of 2 years and may be a major source of gamma radiation in the first 20 years after discharge. Caesium-135 is a long-lived fission product with much weaker radioactivity. Neutron capture inside the reactor transmutes much of the xenon-135 that would otherwise decay to Cs-135. Caesium-137, with a half-life of 30 years, is the main medium-lived fission product, along with Sr-90. Cs-137 is the primary source of penetrating gamma radiation from spent fuel from 10 years to about 300 years after discharge. It is the most significant radioisotope left in the area around Chernobyl.
3 August – Dogxim, the now-dead first known hybrid of a fox and a domesticated dog, discovered in the wild in Brazil in 2021, is reported. 8 August Walking more than 3,967 steps each day is shown to reduce the risk of dying prematurely of any cause, based on a study of 226,000 people around the world. This is considerably less than previous recommendations, which have sometimes cited a figure of 10,000+ steps being needed each day. A study shows activating astrocyte cells in mice with a novel technique makes them stay awake for much longer without making them sleepier or impacting cognition-associated EEG markers. 10 August – Scientists at Fermilab report the most precise measurement yet of the magnetic moment of the muon. The particles are shown to wobble faster than predicted by the Standard Model, hinting at a possible fifth fundamental force. 11 August The rise in photosynthesis rates around the world caused by the increase of carbon dioxide is found to have slowed dramatically in the 21st century, as the atmosphere has grown drier. A global consortium releases two studies and a database on DNA methylation profiles across 348 mammalian species for use in epigenetic clocks. They provide various new results relating to human aging and animal experiments as well as predictive models that can estimate mammalian tissue age or risk with high accuracy. On 16 August, a study indicates chest radiographs evaluated using AI could be a performant biomarker for aging clocks.
Freeze-dried ice cream, also called astronaut ice cream or space ice cream, is ice cream that has had most of the water removed from it by a freeze-drying process. Compared to regular ice cream, it can be kept at room temperature without melting, is dry and more brittle and rigid, but still soft when bitten into. It was developed by Whirlpool Corporation under contract to NASA for the Apollo missions. However, it was not used on any Apollo mission. Freeze-dried foods were developed so that foods could be sent on long-duration spaceflights (e.g. to the Moon), and to reduce the weight of the water and oxygen (which both play a significant role in food deterioration) normally found in food. The process of freeze-drying also eliminates the possibility of food melting and spilling as liquid in zero-gravity, which would be difficult to manage during missions. Freeze-drying (or lyophilization) removes water from the ice cream by lowering the air pressure to a point where ice sublimates directly from a solid to a gas. The ice cream is first placed in a vacuum chamber and frozen until any remaining water crystallizes. The air pressure is then lowered below water's triple point, creating a partial vacuum, forcing air out of the chamber; next, heat is applied, sublimating the ice; finally a freezing coil traps and turns the vaporized water into ice. This process continues for hours, resulting in a freeze-dried ice cream slice.
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.
冻融过程中冰晶形成与局部浓度升高会促使肽链发生界面吸附和聚集。聚集不仅降低有效含量，还会改变可见异物与不溶性微粒的计数结果。将溶液分装为单次使用的小体积等份可减少循环次数。