The short version of dual agonist fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-03-14. Anything still debated is marked as such rather than presented as settled.
Reported outcomes in large trials include dose-dependent weight reduction and improvements in glycemic markers over periods ranging from several months to more than a year. Whether the compound alters long-term cardiovascular or renal outcomes is being examined in dedicated outcome studies, so those questions remain open. Labeling describes gastrointestinal effects such as nausea and diarrhea, which tend to appear during dose escalation. Discontinuation rates and the durability of effects after treatment stops vary across study populations and are still debated.
Tirzepatide is a synthetic peptide developed as a dual agonist at the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. Its structure is built on a GIP-derived backbone with non-natural amino acid substitutions and a fatty diacid side chain that promotes albumin binding and slows clearance. That modification supports once-weekly subcutaneous dosing. Registrational trial programs reported reductions in body weight and glycated hemoglobin alongside the drug's glycemic effects.
Both receptors are class B G protein-coupled receptors that signal largely through Gs-mediated cyclic AMP production. Activation within pancreatic islets increases glucose-dependent insulin secretion and suppresses glucagon release when glucose is elevated. Outside the pancreas, signaling in the central nervous system and gut appears to influence appetite and gastric emptying. The relative contribution of each receptor to observed clinical effects remains under investigation, and the two pathways are not simply additive in practice.
脂肪酸侧链的存在使该肽与血浆白蛋白结合能力增强，从而延长循环半衰期，支持每周一次给药的用药间隔。白蛋白结合同时改变组织分布特征，减慢肾脏清除速度。该设计思路在多种长效肽类药物中被反复采用，属于既定的药代动力学策略。
该化合物的名称与结构由国际非专利名称体系统一维持，不同文献中出现的同义写法主要在拼写顺序或盐形式描述上不同。研究者通常通过受体结合实验、细胞内环磷酸腺苷积累测定以及动物模型来确认其双激动活性。相当一部分分子层面的细节——例如两条受体通路之间的信号交叉作用——尚处于开放问题状态。
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。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic 39-residue peptide | GIP-derived backbone with non-natural residues |
| Molar mass | Approximately 4.8 kDa | Peptide chain plus linker and lipid modifications |
| Appearance | White to off-white powder | Typical of lyophilized research material |
| Solubility | Soluble in water and aqueous buffer | Practically insoluble in nonpolar solvents |
| Storage temperature | Typically −20 °C for dry powder | Solutions usually held at 2–8 °C short term |
Research-grade material circulates through suppliers that differ widely in documentation and testing practice, so a certificate of analysis is a starting point rather than proof of quality. Independent verification typically repeats chromatographic purity and mass confirmation on the received lot, and compares results against a retained reference standard. Regulatory status varies by jurisdiction, and a substance cleared as a medicine is not interchangeable with a research chemical of the same name. Open questions include how closely non-pharmaceutical lots match approved material in impurity profile and in aggregate content.
Solid tirzepatide is handled as a lyophilised, hygroscopic peptide powder that should be kept desiccated, protected from light, and stored frozen, typically at or below minus twenty degrees Celsius for long-term retention. Material left at ambient temperature for extended periods can take up moisture, which promotes aggregation and deamidation. Commercial liquid presentations are kept refrigerated between two and eight degrees Celsius and are not frozen. Reconstituted laboratory solutions are generally held cold and used within a short window because hydrolysis and oxidation continue slowly in solution.
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.
Regulatory and quality discussions place the peptide within established guidance for synthetic peptides and biologics. Forced degradation studies, in which samples are exposed to heat, acid, base, peroxide, and light, identify likely degradation products and validate the selectivity of analytical methods. Reference standards allow comparison across laboratories and production batches. Purity specifications reported in the literature usually combine chromatographic purity with mass confirmation. Which impurity thresholds are meaningful for long-term behavior is still debated, and no single universal specification has been adopted across all jurisdictions.
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 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.
At the receptor level, tirzepatide activates both the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Both belong to the class B family of G protein-coupled receptors and signal largely through cyclic AMP accumulation. The compound binds the two receptors with differing affinity, and the pattern of signaling at each site is described in the literature as biased rather than simply proportional to occupancy. Tissues carrying these receptors include pancreatic islets, adipose tissue, the central nervous system, and the gastrointestinal tract. The relative weight of each receptor population in producing metabolic effects continues to be studied.
Published work supports the view that engaging two incretin receptors produces changes in glucose handling and body weight larger than those seen with single-receptor activation. Why that difference arises is not fully settled. Open questions include how much of the observed weight effect depends on central versus peripheral signaling, and whether the two receptors form interacting complexes. Most reported findings come from controlled trials and animal models, and translation between species is imperfect. Further research is expected to refine these points over time.
ACC Synthase is 450-516 amino acid long sequence depending on the species of plant from which it is extracted. Though it is comparable in the species in which it is found, its COOH-terminal domain is more variable, leading to differences such as oligomerization. The COOH-terminal domain is responsible for oligomerization. In most ACC Synthase producing cells, ACC Synthase exists as a dimer. However, in some we find a monomer ("which is more active and efficient [than its dimer counterpart"). The structure of ACS has been largely determined via X-ray crystallography. Conservation of the residues in ACS's catalytic domain and sequence homology suggest that ACS catalyzes the synthesis of ACC in a similar fashion as other enzymes that require PLP as a cofactor. However, unlike many other PLP-dependent enzymes, Lys (278) is not the only residue that interacts with the substrate. The proximity of the electronegative oxygen from Tyr (152) to the C-γ-S bond suggests a crucial role in the formation of ACC. X-ray crystallography with aminoethoxyvinylglycine (AVG) a competitive inhibitor confirmed Tyrosine's role in the γ elimination. As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes PDB: 1B8G, PDB: 1IAX, PDB: 1IAY, PDB: 1M4N, PDB: 1M7Y, and PDB: 1YNU.
Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994. They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction. The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), the CA1-3 DNAzymes (copper-specific), the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific). The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.
Public health authorities in Western Australia issued an emergency alert for a stretch of road measuring about 1,400 kilometres (870 miles) after a capsule containing caesium-137 was lost in transport on 25 January 2023. The 8 millimetres (0.3 inches) capsule contained a small quantity of the radioactive material when it disappeared from a truck. The State Government immediately launched a search, with the WA Department of Health's chief health officer Andrew Robertson warning an exposed person could expect to receive the equivalent of "about 10 X-rays an hour". Experts warned, if the capsule were found, the public should stay at least 5 metres (16 feet) away. The capsule was found on 1 February 2023.
=== No development reported === Atomoxetine/orexin antagonist (AD-182) – combination of atomoxetine (norepinephrine reuptake inhibitor) and an orexin receptor antagonist [24] Daridorexant (ACT-541468; nemorexant; Quviviq) – orexin OX1 and OX2 receptor antagonist [25] Lemborexant (Dayvigo; E-2006; LEM) – orexin OX1 and OX2 receptor antagonist [26] Research programme: AMPA receptor agonists - RespireRx (ampakines; CX compounds) – ampakines (AMPA receptor positive allosteric modulators) and brain-derived neurotrophic factor (BDNF) stimulants [27] Research programme: sleep apnoea therapeutics - Apnimed – undefined mechanism of action [28] Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist [29] Vornorexant (ORN-0829; TS-142) – orexin OX1 and OX2 receptor antagonist [30]
Sources: en.wikipedia.org
== Clinical trials == The drug is currently under development by AbbVie. Navitoclax is used as mono-therapy as well as in combination with chemotherapies (paclitaxel, docetaxel, gemcitabine, and irinotecan), olaparib, erlotinib, venetoclax, and rituximab in advanced hematological malignancies (in both pediatric and adult patients) and solid tumors including ovarian cancer, breast cancer, lung cancer. Additionally, an ongoing global multi-center, randomized, open-label, phase 3 study evaluating efficacy and safety of navitoclax in combination with ruxolitinib versus best available therapy in adult patients with relapsed/refractory myelofibrosis was initiated on 31 August 2020. The study is expected to conclude in 2026.
The tea served on New Year's Day and at weddings is sometime kelp tea because the pronunciation of kombu is similar to that of the last part of "yorokobu" (喜ぶ, meaning "be happy"). Fuku-cha(福茶, meaning "fortune tea") is sencha green tea with kombu, umeboshi (pickled plum), kuromame (black beans), and sanshō (Japanese pepper) and is drunk on the last day of the year (Ōmisoka), in New Year, and on the day before the beginning of spring (Setsubun) in Kansai region, wishing a long life. In particular, in New Year, oo-buku-cha or dai-buku-cha (大福茶, meaning "very good fortune tea"), which is sencha green tea with kombu and umeboshi, is drunk in Kansai region wishing good health and happiness.
Gaza war: David Cameron, the new foreign secretary, announces sanctions against four senior Hamas leaders and two of the militant group's financiers. Chelsea Ladies Football Club manager Emma Hayes is named as the new manager of the United States women's national football team, and will take up the role in May 2024. 15 November Inflation falls to 4.6%, the lowest rate since November 2021, driven mainly by lower energy prices. The British Government's plan to deport migrants to Rwanda is ruled as unlawful by the Supreme Court. Sunak says the government will introduce "emergency legislation" to enable Parliament to "confirm Rwanda is safe" and prevent legal challenges from blocking the migrant policy. More than 50 Labour MPs defy Sir Keir Starmer to vote for an immediate ceasefire in the Israel-Hamas war. The General Synod of the Church of England votes to allow special church services of blessing for gay couples. 16 November David Cameron makes his first working visit to Ukraine as foreign secretary, where he meets President Volodymyr Zelensky in Kyiv, and reiterates the UK's promise to provide moral, diplomatic and "above all military support for... however long it takes". Train drivers union ASLEF announces new strike dates, with a rolling programme of strikes from 2 to 8 December affecting different train companies on different days. A sixth person is confirmed dead following a house fire in Hounslow, West London.
2006: Chilean biochemist Cecilia Hidalgo Tapia became the first woman to receive the Chilean National Prize for Natural Sciences. 2006: Chinese-American biochemist Yizhi Jane Tao led a team of researchers to become the first to map the atomic structure of Influenza A, contributing to antiviral research. 2006: Parasitologist Susan Lim became the first Malaysian scientist elected to the International Commission on Zoological Nomenclature. 2006: Merieme Chadid became the first Moroccan person and the first female astronomer to travel to Antarctica, leading an international team of scientists in the installation of a major observatory in the South Pole. 2006: American computer scientist Frances E. Allen won the Turing Award for "pioneering contributions to the theory and practice of optimizing compiler techniques that laid the foundation for modern optimizing compilers and automatic parallel execution". She was the first woman to win the award. 2006: Israeli crystallographer Ada E. Yonath became the first woman awarded the Wolf Prize in Chemistry for "ingenious structural discoveries of the ribosomal machinery of peptide-bond formation and the light-driven primary processes in photosynthesis." 2006: Canadian-American computer scientist Maria Klawe became the president of Harvey Mudd College. 2007: Using satellite imagery, Egyptian geomorphologist Eman Ghoneim discovered traces of an 11,000-year-old mega lake in the Sahara Desert. The discovery shed light on the origins of the largest modern groundwater reservoir in the world.
==== Studio albums ==== American Drift (2015, Blueberry Recordings) Elysia Crampton Presents: Demon City (2016, Break World Records) Spots y Escupitajo (2017, The Vinyl Factory) Elysia Crampton (2018, Break World Records) Orcorara 2010 (2020, PAN)
Sources: en.wikipedia.org
It acts as an agonist at both the GIP and GLP-1 receptors, two related class B G protein-coupled receptors. This dual activity distinguishes it from single-receptor GLP-1 agonists. The clinical consequences of engaging both receptors are still being characterized.
It is given by subcutaneous injection, generally on a weekly schedule. Dosing usually begins low and increases in steps to limit gastrointestinal side effects. Formulated product is supplied as a ready-to-use pen or vial in most markets.
No. Receptor engagement is documented, but how central appetite circuits, gut signals, and insulinotropic effects combine is incompletely resolved. Investigators continue to separate GIP-driven from GLP-1-driven contributions in animal and human models.
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。