Everything below concerns Incretin hormone. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-07-29. Numbers and descriptions here follow the published literature rather than marketing material.
当前公开资料把 tirzepatide 归为肠促胰素类受体双重激动剂。它并非激素天然变体，而是经过序列改造的工程化肽。其分子量、等电点与疏水性等基础参数已在药典和化学数据库中收录，可作为分析检测和质量研究的参照。
Tirzepatide 是一种由 39 个氨基酸组成的合成肽，分子结构上以 GIP 序列为骨架并引入脂肪酸侧链修饰，使其能够同时与葡萄糖依赖性促胰岛素多肽（GIP）受体和胰高血糖素样肽-1（GLP-1）受体结合。这种双重激动特性使它在同类肽类药物中区别于选择性 GLP-1 受体激动剂。该分子最早由一家制药公司在 2010 年代报道，随后进入糖尿病与体重管理领域的临床研究。
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 |
|---|---|---|
| 分子类型 | 合成修饰肽 | 39 个氨基酸，含脂肪酸侧链 |
| 受体靶点 | GIP 与 GLP-1 受体 | 双重激动剂 |
| 分子量 | 约 4.8 kDa | 以游离肽计 |
| 外观 | 白色至类白色粉末 | 冻干形态常见 |
| 溶解性 | 可溶于水及水性缓冲液 | 溶解后宜低温保存 |
Like most synthetic peptides of this size, the material is commonly supplied as a lyophilised powder that appears white to off-white. It dissolves in aqueous buffers and in mixtures of water with a small proportion of organic solvent, though the fatty acid portion reduces solubility in pure water relative to short peptides. Hygroscopic behaviour is reported for many peptide powders, so weighing is usually performed quickly and under controlled humidity. Working solutions are typically prepared fresh and kept cold.
Long-term storage of lyophilised peptide powder is generally at minus twenty degrees Celsius or colder, with desiccant and protection from light. Short-term storage at two to eight degrees Celsius is common during active use. In solution, stability depends strongly on pH, concentration, and the presence of preservatives, and hydrolysis or aggregation can develop over weeks. Published stability data specific to this molecule are limited, so recommended conditions for research material are usually extrapolated from general peptide handling practice rather than from a dedicated study.
Bulk peptide material is normally characterised by reversed-phase high-performance liquid chromatography, which separates the target sequence from truncation products and other closely related impurities. Ultraviolet detection near 214 nanometres is common because the peptide backbone absorbs in that region. Mass spectrometry, usually electrospray ionisation coupled to a mass analyser, is used to confirm the molecular mass. Because the molecule carries a lipophilic side chain, gradient methods often need a relatively high organic modifier fraction to elute it within a practical retention window.
Routine characterization of the peptide relies on reversed-phase high-performance liquid chromatography for purity assessment, usually with ultraviolet detection near 214 nanometers. Intact mass measurement by liquid chromatography coupled to mass spectrometry confirms molecular identity against a theoretical value. Sequence-level confirmation uses enzymatic digestion followed by tandem mass spectrometry, an approach known as peptide mapping. Amino acid analysis gives an independent check on composition. Circular dichroism spectra are used to estimate helical content in aqueous buffer.
Stability depends strongly on physical form. The dry powder is generally regarded as stable for extended periods when held at or below minus twenty degrees Celsius in a sealed, desiccated container. In solution, degradation pathways include deamidation of asparagine and glutamine residues, oxidation of methionine, and aggregation. Reaction rates for these pathways rise with temperature. Repeated freezing and thawing of solutions promotes aggregation, and light exposure can accelerate some oxidative changes. Buffer composition and pH influence which pathway dominates at a given temperature.
The molecule is a synthetic 39-amino-acid peptide whose backbone derives from the sequence of human glucose-dependent insulinotropic polypeptide, with several substitutions that raise metabolic stability and shift receptor preference. A C20 fatty diacid is attached through a short linker to a lysine side chain, a modification that increases binding to serum albumin. The reported monoisotopic mass is approximately 4813 Da. Near neutral pH the peptide carries a net negative charge, and the lipid tail makes the molecule markedly more hydrophobic than the unmodified parent sequence.
Dual agonism at the GIP and GLP-1 receptors underlies the observed pharmacology. Activation of GLP-1 receptors raises glucose-dependent insulin release, lowers glucagon secretion, slows gastric emptying and reduces appetite. GIP receptor activation contributes additional effects on adipose tissue and on energy balance, and the combined action on appetite appears larger than either pathway alone in animal models. Signalling bias and the relative contribution of each receptor arm to weight-related effects remain areas of active investigation.
Structure-activity work shows that fatty acid length, linker chemistry and the position of acylation all influence albumin affinity and receptor potency. Plasma protein binding exceeds 99 percent, which restricts distribution and slows renal clearance. Degradation proceeds largely through general proteolysis and fatty acid oxidation rather than cytochrome P450 metabolism, so exposure to common oxidative drug interactions is limited. Whether these clearance routes vary meaningfully between individuals is not fully established.
At the receptor level, the compound binds both GIP and GLP-1 receptors and triggers downstream signalling that raises cyclic AMP in target cells. GLP-1 receptor activation is associated with glucose-dependent insulin release, slower gastric emptying, and reduced appetite signalling. GIP receptor activation contributes effects that are less completely characterised, and how much each receptor adds to the overall clinical response is still an open question. The two pathways appear to interact in a complementary rather than a purely additive way.
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.
=== Location === It may be found in tissue sections from almost every part of the body. It surrounds blood vessels and nerves and penetrates with them even into the small spaces of muscles, tendons, and other tissues. It may likewise be present in the mediastinal extremities. Nearly every epithelium rests on a layer of areolar tissue, whose blood vessels provide the epithelium with nutrition, waste removal, and a ready supply of infection-fighting leukocytes when needed. Because of the abundance of open, fluid-filled space, leukocytes can move about freely in areolar tissue and can easily find and destroy pathogens. The areolar tissue is found beneath the epidermis layer and is also underneath the epithelial tissue of all the body systems that have external openings. it makes the skin elastic and helps it to withstand pulling pain. It is also a component of the lamina propria of the digestive and respiratory tracts, the mucous membranes of reproductive and urinary systems, the stroma of glands, and the hypodermis of the skin. It is also found in the mesentery which is surrounding the intestine.
solubility The property of a solid, liquid, or gaseous solute to dissolve in a solid, liquid, or gaseous solvent. It is typically expressed as the proportion of solute dissolved in the solvent in a fully saturated solution.
Composed of three branches, all headquartered in Washington, D.C., the federal government is the national government of the United States. The U.S. Constitution establishes a separation of powers intended to provide a system of checks and balances to prevent any of the three branches from becoming supreme. The three-branch system is known as the presidential system, in contrast to the parliamentary system where the executive is part of the legislative body. Many countries around the world adopted this aspect of the 1789 Constitution of the United States, especially in the postcolonial Americas.
A Novichok agent was used in 1995 to poison Russian banker Ivan Kivelidi, who died three days later in a hospital at the age of 46. The poison was believed to have been applied to Kivelidi's office phone in Moscow. His secretary Zara Ismailova also developed symptoms one month later and then died a day later in a hospital at the age of 35. Kivelidi was the head of the Russian Business Round Table, and had close ties to Viktor Chernomyrdin, who was at that time Prime Minister of Russia. Russian opposition–linked historians Yuri Felshtinsky and Vladimir Pribylovsky speculated that the murder became "one of the first in the series of poisonings organised by Russia's security services". The Russian Ministry of Internal Affairs analysed the substance and announced that it was "a phosphorus-based military-grade nerve agent" "whose formula was strictly classified". According to Nesterov, the administrative head of Shikhany, he did not know of "a single case of such poison being sold illegally" and noted that the poison "is used by professional spies". Vladimir Khutsishvili, a former business partner of Kivelidi's, was subsequently convicted of the killings. According to The Independent, "A closed trial found that his business partner had obtained the substance via intermediaries from an employee of the State Research Institute of Organic Chemistry and Technology (ГосНИИОХТ / GosNIIOKhT), which was involved in the development of Novichok agents. However, Khutsishvili, who claimed that he was innocent, had not been detained at the time of the trial and freely left the country.
The report concluded that a final determination of the origin was unlikely without cooperation from the Chinese government, saying their prior lack of transparency "reflect[ed] in part China's government's own uncertainty about where an investigation could lead, as well as its frustration that the international community is using the issue to exert political pressure on China." Chinese foreign ministry spokesman Wang Wenbin said that the US intelligence report was "unscientific and has no credibility". On 23 May 2021, The Wall Street Journal reported that a previously undisclosed US intelligence report stated that three researchers from the Wuhan Institute of Virology became ill enough in November 2019 to seek hospital care. The report did not specify what the illness was. Officials familiar with the intelligence differed as to the strength to which it corroborates the hypothesis that the virus responsible for COVID-19 was leaked from the WIV. The WSJ report notes that it is not unusual for people in China to go to the hospital with uncomplicated influenza or common cold symptoms. Yuan Zhiming, director of the WIV's Wuhan National Biosafety Laboratory, responded in the Global Times, a Chinese state media outlet, that the "claims are groundless". Marion Koopmans, a member of the WHO study team, described the number of flu-like illnesses at the WIV in 2019 as "completely normal". Workers at the WIV must provide yearly serum samples. WIV virologist Shi Zhengli said in 2020 that, based on an evaluation of those serum samples, all staff tested negative for COVID-19 antibodies.
Sources: en.wikipedia.org
=== Trump administrations === President Donald Trump used the IEEPA extensively, sanctioning more than 3,700 entities and invoking 11 national emergency declarations (out of the 13 that he declared overall) relying primarily or exclusively on IEEPA authority during his 2017–21 term; Trump also used or threatened use of its powers in unconventional and unprecedented manners (including executive actions utilizing powers under the act that prompted legal challenges). On May 30, 2019, the White House announced that Trump would use IEEPA powers to introduce tariffs on imports from Mexico in response to the national security threat of illegal immigration from Mexico into the United States. As part of an ongoing trade war with China, on August 24, 2019, Trump tweeted that he "hereby ordered" U.S. companies to start looking at alternatives to China on the basis of claimed powers under IEEPA. Trump, however, did not formally declare an emergency as required by IEEPA. In September 2020, the Trump administration sanctioned and imposed visa restrictions on two International Criminal Court (ICC) officials, prosecutor Fatou Bensouda and Jurisdiction Complementarity and Cooperation Division Director Phakiso Mochochoko, over the court's investigation into allegations of war crimes committed by the U.S. and Israel in Afghanistan and the Palestinian territories, respectively.
When used as a seed treatment or seed coating on cotton, corn, seed potatoes, soybeans, sugar beets, tomatoes, wheat, and many other seeds, it elicits an innate immunity response in developing roots which destroys parasitic cyst nematodes without harming beneficial nematodes and organisms. Agricultural applications of chitosan can reduce environmental stress due to drought and soil deficiencies, strengthen seed vitality, improve stand quality, increase yields, and reduce fruit decay of vegetables, fruits and citrus crops . Horticultural application of chitosan increases blooms and extends the life of cut flowers and Christmas trees. The US Forest Service has conducted research on chitosan to control pathogens in pine trees and increase resin pitch outflow which resists pine beetle infestation. Chitosan has been studied for applications in agriculture and horticulture dating back to the 1980s. By 1989, chitosan salt solutions were applied to crops for improved freeze protection or to crop seed for seed priming. Shortly thereafter, chitosan salt received the first ever biopesticide label from the EPA, then followed by other intellectual property applications. Chitosan has been used to protect plants in space, as well, exemplified by NASA's experiment to protect adzuki beans grown aboard the space shuttle and Mir space station in 1997. NASA results revealed chitosan induces increased growth (biomass) and pathogen resistance due to elevated levels of β-(1→3)-glucanase enzymes within plant cells. NASA confirmed chitosan elicits the same effect in plants on earth.
In 2021, FAO released the first definition of agrifood systems and agrifood systems' resilience in The State of Food and Agriculture 2021 – Making agrifood systems more resilient to shocks and stresses. The definition of agrifood systems' resilience is adapted from Tendall et al.'s definition of food system resilience, which is "capacity over time of a food system and its units at multiple levels, to provide sufficient, appropriate and accessible food to all, in the face of various and even unforeseen disturbances". Agrifood systems are broader than food systems, as these encompass the entire range of actors and their interlinked value-adding activities in the primary production of food and non-food agricultural products, as well as in food storage, aggregation, post-harvest handling, transportation, processing, distribution, marketing, disposal and consumption.
== Applications == Structural steel to keep below critical temperature ca. 540 °C Electrical circuits to keep critical electrical circuits below 140 °C so they stay operational Liquified petroleum gas containers to prevent a BLEVE (boiling liquid expanding vapour explosion) Vessel skirts and pipe bridges in an oil refinery or chemical plant to keep the structural steel below critical temperature ca. 540° Concrete linings of traffic tunnels Fireblocking: In a wood frame construction, gaps are created by joists or studs in floor or wall partitions. These hollow spaces allow fire to travel easily from one area to another. Fireblocks are installed internally to divide these areas into smaller intervals. Common materials used include solid lumber, plywood, OSB, Particle board, gypsum board, cement fiberboard, or glass fiber insulation batts. Firewall (construction) is a common method employed to separate a building into small units to restrict or delay the spread of fire from one section to the next. Fire walls usually extend the full length of a building, from foundation to roof. Fire barriers and fire partitions: They are similar to fire walls in operation; however, their height is limited to a single floor, from the slab of one floor to the underside of the next. Coatings, e.g. to fireproof wood.
Sources: en.wikipedia.org
After Commodore Perry opened up trade with Japan in 1854, Japanese green tea became the bulk of America’s tea imports. The 19th century saw the rise of iced tea, especially in the South. One of the earliest recipes for American iced tea appeared in Housekeeping in Old Virginia, a cookbook from 1879. It stated: “After scalding the teapot, put into it one quart of boiling water and two teaspoonfuls of green tea. ... Fill the goblets with ice and sugar. A squeeze of lemon will make this delicious and healthful, as it will correct the astringent tendency.” Alcoholic iced tea punches with cream, sugar, and liquor also became popular in the 19th century, especially in southern towns like Charleston and Savannah. These iced tea drinks resemble the modern Sweet bourbon punch and Long Island iced tea. Fish house punch was often also diluted with tea. The 19th century also saw the growth of various tea companies, like The Great American Tea Company, later renamed The Great Atlantic & Pacific (A&P) and the Oriental & Occidental Tea Company. During the hot days of the 1904 World's Fair in St. Louis, iced tea became the most popular drink at the fair among its 20 million visitors. This was a major moment in the rise in popularity of American iced tea. Prohibition (1920–1933) saw the rise of non-alcoholic iced teas, as clubs, hotels and other venues sought to re-stock their drink menus with other strong flavorful drinks. The introduction of the home refrigerator (1920s and '30s) also made it much easier for iced tea to be made at home.
RYB (an abbreviation of red–yellow–blue) is a subtractive color model used in art and applied design in which red, yellow, and blue pigments are considered primary colors. Under traditional color theory, this set of primary colors was advocated by Moses Harris, Michel Eugène Chevreul, Johannes Itten and Josef Albers, and applied by countless artists and designers. The RYB color model underpinned the color curriculum of the Bauhaus, Ulm School of Design and numerous art and design schools that were influenced by the Bauhaus, including the IIT Institute of Design (founded as the New Bauhaus), Black Mountain College, Design Department Yale University, the Shillito Design School, Sydney, and Parsons School of Design, New York. In this context, the term primary color refers to three exemplar colors (red, yellow, and blue) as opposed to specific pigments. As illustrated, in the RYB color model, red, yellow, and blue are intermixed to create secondary color segments of orange, green, and purple. This set of primary colors emerged at a time when access to a large range of pigments was limited by availability and cost, and it encouraged artists and designers to explore the many diverse colors through mixing and intermixing a limited range of pigment colors. In art and design education, gray, red, yellow, and blue pigments were usually augmented with white and black pigments, enabling the creation of a larger gamut of colors and details including tints and shades.
In 1991, the Proceeds of Crime (Money Laundering) Act was brought into force in Canada to give legal effect to the former FATF Forty Recommendations by establishing record keeping and client identification requirements in the financial sector to facilitate the investigation and prosecution of money laundering offences under the Criminal Code and the Controlled Drugs and Substances Act. In 2000, the Proceeds of Crime (Money Laundering) Act was amended to expand the scope of its application and to establish a financial intelligence unit with national control over money laundering, namely FINTRAC. In December 2001, the scope of the Proceeds of Crime (Money Laundering) Act was again expanded by amendments enacted under the Anti-Terrorism Act with the objective of deterring terrorist activity by cutting off sources and channels of funding used by terrorists in response to 9/11. The Proceeds of Crime (Money Laundering) Act was renamed the Proceeds of Crime (Money Laundering) and Terrorist Financing Act. In December 2006, the Proceeds of Crime (Money Laundering) and Terrorist Financing Act was further amended, in part, in response to pressure from the FATF for Canada to tighten its money laundering and financing of terrorism legislation.
Sources: en.wikipedia.org
它属于合成修饰肽，同时激动 GIP 与 GLP-1 两种肠促胰素受体。这类分子通常被称为双重肠促胰素受体激动剂，与选择性 GLP-1 激动剂在靶点范围上不同。
分子上的脂肪酸侧链使其与血浆白蛋白结合增强，显著延长循环半衰期。半衰期延长后，稳定血药浓度可在较长的给药间隔内维持，因此常见用法为每周一次。
同时激活两条肠促胰素通路可能在胰岛素分泌、胃排空和食欲调节上产生叠加效应。与单靶点相比，临床研究中观察到的血糖与体重变化幅度通常更明显，但各通路的具体贡献比例尚无定论。
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.