The short version of 稳定性 fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-08-15. Anything still debated is marked as such rather than presented as settled.
An extended fatty diacid moiety promotes binding to serum albumin, which slows renal clearance and extends the circulating half-life to roughly five days. That property supports once-weekly administration and largely explains the dosing interval described in clinical reports. Published data come mainly from large randomised programmes that evaluated glycaemic control and body weight over periods of many months. Long-term outcomes beyond those trial windows, including what happens after treatment stops, remain an active area of investigation.
Tirzepatide is a synthetic peptide built from thirty-nine amino acids. Its sequence is derived from native glucose-dependent insulinotropic polypeptide, or GIP, with several non-natural residues and a fatty diacid side chain attached through a linker. The molecule behaves as a dual agonist at two incretin receptors, GIP and GLP-1, instead of targeting a single receptor. This dual engagement separates it from earlier single-receptor incretin compounds and underpins most of its reported pharmacological activity.
The peptide activates two G protein-coupled receptors, GIPR and GLP-1R. Binding triggers adenylyl cyclase activity and raises intracellular cyclic AMP in pancreatic beta cells, which potentiates insulin release when glucose is elevated. Signaling in the central nervous system is associated with reduced appetite and lower energy intake, while effects on gastric emptying and glucagon secretion are also reported. Because activity at both receptors is retained, the pharmacological profile is often described as incretin-based rather than selective for a single receptor.
After subcutaneous injection, absorption is gradual, and peak plasma levels are generally reached within one to three days. Albumin binding extends the apparent half-life to roughly five days, which supports a weekly administration schedule. Metabolism proceeds mainly through proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid chain, rather than through cytochrome P450 pathways. Eliminated fragments are largely recycled through general protein turnover, and excretion of intact drug in urine is minimal. These properties distinguish the molecule from short-acting incretin mimetics.
Tirzepatide is a synthetic peptide of 39 amino acids engineered from the native glucose-dependent insulinotropic polypeptide sequence. Its structure incorporates several non-natural residues and a C-terminal segment derived from glucagon-like peptide-1, together with a C20 fatty diacid moiety attached through a linker. The lipophilic side chain promotes binding to serum albumin, which slows renal clearance after administration. The compound is classified as a dual incretin receptor agonist and is supplied as a lyophilized powder for reconstitution or as a preformulated solution, depending on the presentation.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C225H348N48O68 | Free base form |
| Molecular mass | Approximately 4813 Da | Calculated from the sequence |
| Amino acid residues | 39 | GIP-derived backbone |
| Receptor targets | GIP and GLP-1 | Dual agonist |
| Circulating half-life | About 5 days | Supports weekly administration |
溶解操作一般使用注射用水或适宜的水性缓冲液，必要时加入少量助溶剂以改善溶解速度，但应避免剧烈涡旋振荡，因为剪切力可能促进聚集。配制后的溶液在冷藏条件下的稳定时间通常短于固体形态，具体时限取决于浓度、缓冲体系与容器材质。是否加入防腐成分，则取决于用途是否为多次取样。
定量分析的主流方法是反相高效液相色谱联用紫外或质谱检测，利用肽在疏水固定相上的保留行为确定纯度与含量。对于生物基质中的浓度测定，常采用液相色谱串联质谱，并配合固相萃取或蛋白沉淀进行样品前处理。免疫分析法也可使用，但可能受到结构相关肽的交叉反应干扰。
Tirzepatide is a synthetic peptide of 39 amino acids that carries a C20 fatty diacid side chain attached through a linker. Its molecular formula is C225H348N48O68, and its molecular weight is about 4813 daltons. The compound belongs to the incretin mimetic class and is administered by subcutaneous injection. The fatty acid chain promotes binding to serum albumin, which slows renal clearance and extends the circulation time of the molecule. It was identified during screening of sequences derived from glucose-dependent insulinotropic polypeptide.
Tirzepatide activates both the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor, making it a dual agonist rather than a selective agent. Engagement of the GLP-1 receptor is linked to glucose-dependent insulin release, slower gastric emptying, and reduced appetite signalling. The relative contribution of the GIP arm remains an active research question; proposed roles include improved insulin sensitivity and altered adipose tissue handling. Receptor occupancy studies suggest the molecule interacts with both targets at circulating concentrations achieved during therapy.
Development began in the 2010s, when researchers modified a GIP-based scaffold to add GLP-1 activity and then attached the fatty diacid to lengthen its half-life. Clinical evaluation proceeded through large phase 3 programmes in type 2 diabetes and in obesity, and regulators in the United States cleared the compound for type 2 diabetes in 2022 and for chronic weight management in 2023. Several cardiovascular and metabolic outcome studies are still reporting, so the picture of long-term benefit and risk is incomplete. Approvals in other regions followed on different timelines.
Tirzepatide is a synthetic peptide built from 39 amino acid residues. Its backbone derives from the native glucose-dependent insulinotropic polypeptide sequence, altered at several positions to resist enzymatic cleavage. A fatty diacid group attached through a linker extends plasma residence time by promoting reversible binding to serum albumin. The molecule carries a net negative charge near physiological pH and has a reported molecular weight close to 4813 daltons. These features separate it from shorter incretin analogs and account for its prolonged dosing interval.
Pharmacologically, tirzepatide activates two distinct G protein-coupled receptors: the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Binding at each target triggers cyclic AMP accumulation and downstream signaling in pancreatic beta cells, adipose tissue and the central nervous system. Because the two pathways overlap only partially, the combined effect on insulin secretion, glucagon suppression and appetite signaling differs from that of selective single-receptor compounds. Affinity is not equal across the two targets, and the clinical meaning of that imbalance remains an area of active study.
Mils and strecks are small units of angle used by various military organizations for range estimation and translating map coordinates used for directing artillery fire. The exact size varies between different organizations: there are 6400 NATO mils per turn (1 NATO mil = 0.982 mrad), or 6000 Warsaw pact mils per turn (1 Warsaw pact mil = 1.047 mrad). In the Swedish military, there are 6300 strecks per turn (1 streck = 0.997 mrad).
Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting. The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or guanosine triphosphate (GTP), effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation.
In the age of nationalism, Protestant Germans, whether Conservative (like Otto von Bismarck) or Liberal, accused the Centre of Ultramontanism or having a greater loyalty towards the Pope than to the German nation. After the First Vatican Council, Bismarck launched the Kulturkampf ("cultural struggle") against the Catholic Church. Catholics fought back vigorously and with near-unanimity. The Centre party gained greater support from the Catholic population. Following Bismarck's 1879 turn from free trade to protectionism and from the National Liberal party to the Conservative parties, he also abandoned the unsuccessful Kulturkampf. The Centre party remained a party of opposition to Bismarck, but after his resignation in 1890, it frequently supported the following administrations' policies in the Reichstag, particularly in the field of social security.
=== Infants === The normal range of AFP for adults and children is variously reported as under 50, under 10, or under 5 ng/mL. At birth, normal infants have AFP levels four or more orders of magnitude above this normal range, that decreases to a normal range over the first year of life. During this time, the normal range of AFP levels spans approximately two orders of magnitude. Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns. Very high AFP levels may be subject to hooking (see tumor marker), which results in the level being reported significantly lower than the actual concentration. This is important for analysis of a series of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer survivors, where the rate of decrease of AFP has diagnostic value.
Sources: en.wikipedia.org
== Arthropathies and related disorders (710–719) == 710 Diffuse diseases of connective tissue 710.0 Systemic lupus erythematosus 710.2 Sjögren's syndrome 710.3 Dermatomyositis 710.4 Polymyositis 710.5 Eosinophilia myalgia syndrome 710.9 Connective tissue disease, unspec. 711 Arthropathy associated with infections 712 Crystal arthropathies 712.1 Chondrocalcinosis due to dicalcium phosphate crystals 712.2 Chondrocalcinosis due to pyrophosphate crystals 712.3 Chondrocalcinosis, cause unspecified pseudogout 712.8 Other specified crystal arthropathies 712.9 Unspecified crystal arthropathy 713 Arthropathy, endocrine disorders 713.1 Arthropathy, gastrointestinal conditions 714 Rheumatoid arthritis and other inflammatory polyarthropathies 714.0 Rheumatoid arthritis 714.3 Polyarticular juvenile rheumatoid arthritis 715 Osteoarthrosis and allied disorders 715.09 Osteoarthrosis, generalized, multiple sites 715.11 Osteoarthrosis, shoulder 715.14 Osteoarthrosis, hand 715.15 Osteoarthrosis, hip 715.16 Osteoarthrosis, knee 715.17 Osteoarthrosis, ankle/foot 715.9 Osteoarthrosis, unspec. 716 Other and unspecified arthropathies 716.1 Arthropathy, traumatic, unspec. 716.9 Arthropathy, unspec. 717 Internal derangement of knee 717.1 Derangement of anterior horn of medial meniscus 717.42 Derangement of lateral meniscus 717.7 Chondromalacia of patella 717.9 Derangement, internal, knee, unspec.
=== Dissolved gases === Oxygen dissolved in water can lead to unwanted oxidation of silicon wafers and other materials while gases like carbon dioxide lead to unwanted acidification of water and must be removed. Gases can be removed through various methods including thermal or pressure degassing, membrane degassers or chemical degassing.
Prolargin is a protein that in humans is encoded by the PRELP gene. The protein encoded by this gene is a leucine-rich repeat protein present in connective tissue extracellular matrix. This protein functions as a molecule anchoring basement membranes to the underlying connective tissue. This protein has been shown to bind type I collagen to basement membranes and type II collagen to cartilage. It also binds the basement membrane heparan sulfate proteoglycan perlecan. This protein is suggested to be involved in the pathogenesis of Hutchinson–Gilford progeria (HGP), which is reported to lack the binding of collagen in basement membranes and cartilage. Alternatively spliced transcript variants encoding the same protein have been observed.
Sources: en.wikipedia.org
== Emitters == Several different emitter configurations have been used for FD emitters, such as single tips, sharp blades and thin wires. Single metal tips can be made from etching wires either by periodically dipping them into molten salts or by electrolysis in aqueous solutions. Compared to other emitter types, the single tips have the advantage that they can reach the highest field strengths. In addition, well-defined geometric shape of a single tip allows accurate calculation of the potential distribution in the space between the tip and the counter electrode. For blades used as emitters, their ruggedness under the high electric field is one of their advantages. Different thin wires were also used as emitters, such as platinum wires and tungsten wires. Platinum wires are fragile, and tungsten wires are much more stable than platinum wires. Among those emitters, carbon-microneedles tungsten wires are the most widely used emitters in FD mass spectrometry.
==== IDF's use of white phosphorus ==== On 31 October 2023, after an investigation, Amnesty International stated that an Israeli white phosphorus attack on 16 October was indiscriminate, unlawful, and "must be investigated as a war crime", due to its use on the populated Lebanese town of Dhayra, which injured at least nine civilians. On 2 November, Amnesty International stated its investigations into four incidents on 10, 11, 16 and 17 October showed Israel had used white phosphorus munitions. The claim was confirmed by the Washington Post, which identified two white phosphorus shell casings made in the U.S. Human Rights Watch verified IDF's use of white phosphorus in at least 17 municipalities in Lebanon, including five municipalities where airburst munitions were used over residential areas. It also called on the Lebanese government to file a declaration to enable investigations in the International Criminal Court. In southern Lebanon, Israel's white phosphorus bombs have destroyed over 4,500 hectares (45 million m2) of forest with economic loses being valued at US$20 million. The American University of Beirut estimated use of white phosphorus has led to more than 134 forest fires as of June 2024 burning 1,500 hectares (15 million m2) of land. As of 28 May 2024, the Lebanese Ministry of Public Health said that exposure to white phosphorus had injured at least 173 people.
Originally, seven such proteins were discovered. Of these, six (BMP2 through BMP7) belong to the Transforming growth factor beta superfamily of proteins. BMP1 is a metalloprotease. Since then, thirteen more BMPs, all of which are in the TGF-beta family, have been discovered, bringing the total to twenty. The current nomenclature only recognizes 13, as many others are put under the growth differentiation factor naming instead.
Sources: en.wikipedia.org
It acts as a dual agonist at the GIP receptor and the GLP-1 receptor. This broader targeting profile distinguishes it from selective GLP-1 agonists, which engage only one receptor.
A fatty diacid side chain promotes binding to albumin, which delays clearance from circulation. The half-life of roughly five days makes a weekly schedule practical.
No. It is a synthetic peptide whose backbone is based on the natural incretin hormone GIP. Non-natural residues and the lipid side chain were engineered to improve stability and duration of action.
It is a synthetic linear peptide that acts as a dual agonist at the GIP and GLP-1 receptors. It combines a modified incretin backbone with a fatty diacid side chain that extends its circulation time. It is not a small-molecule drug and is not orally absorbed in its native form.