This is a working overview of Dual agonist, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-08-16. Anything still debated is marked as such rather than presented as settled.
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.
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 formula | C225H348N48O68 | Peptide backbone with a fatty diacid chain |
| Molecular weight | About 4813 Da | Calculated from the formula |
| Receptor targets | GIP and GLP-1 receptors | Dual agonist activity at both sites |
| Route of administration | Subcutaneous injection | No approved oral form at present |
| Elimination half-life | About 5 days | Supports extended intervals between administrations |
Cold-chain handling is standard for formulated product, with dry powder stored frozen and ready-to-use solutions refrigerated. Light exposure is minimized because photodegradation of certain amino acid side chains is possible. Shipping and temperature-excursion studies are used to establish whether short deviations affect quality attributes. Documentation supplied with research material usually includes a certificate of analysis listing purity, identity confirmation, and water or residual solvent content. Users are expected to confirm that material meets the stated specification before use.
Identity and purity of tirzepatide are assessed mainly by reversed-phase high-performance liquid chromatography with ultraviolet detection, often paired with mass spectrometry. Because the molecule carries several modifications, gradient conditions are adjusted to resolve the intact peptide from deamidation and oxidation products. Enzymatic digestion followed by peptide mapping confirms the primary sequence and locates specific modifications. Quantitation in biological matrices typically uses liquid chromatography with tandem mass spectrometry after solid-phase extraction. Immunoassays are used less often, since antibody cross-reactivity with closely related peptides can bias results.
The peptide shares degradation routes common to modified peptides: deamidation of asparagine and glutamine residues, oxidation of methionine, and backbone hydrolysis under extreme pH. Lyophilized material is generally more stable than a solution, and residual water content directly affects the rate of hydrolysis. In liquid form, aggregation and visible particles can appear after agitation or repeated freeze-thaw cycles. Stability studies therefore track monomer content, aggregate content, and potency over months under defined temperature and humidity.
Identity and purity are established with reversed-phase high-performance liquid chromatography, often paired with mass spectrometry for confirmation of the expected mass. Peptide mapping after enzymatic digestion verifies the primary sequence and detects substitutions. Size-exclusion chromatography quantifies aggregates and fragments, which are the impurities most often tracked for peptides of this size. Residual solvents, counterions, and water content fall under separate tests described in pharmacopeial chapters. Circular dichroism or nuclear magnetic resonance may be used in research settings to probe secondary structure, though such methods are less common in routine release testing.
Peptide active ingredients of this type are typically supplied as lyophilized powder because the dry form resists hydrolysis during transport. The material is hygroscopic, so vials are usually equilibrated to room temperature before opening to avoid condensation on the solid. Repeated freeze-thaw cycles can promote aggregation and are generally avoided by aliquoting stock into single-use portions. Personnel handling the powder work in controlled environments to limit inhalation of fine particles. Written procedures usually specify these steps rather than leaving them to individual judgment.
Long-term storage of the solid generally relies on temperatures at or below minus twenty degrees Celsius, while short-term working stocks may be held refrigerated. Light exposure is limited because photodegradation can alter side chains over extended periods. Solutions prepared for analysis are less stable than the dry powder and are typically used within the same working day. Buffer choice matters, since some aqueous conditions favor deamidation or oxidation at specific residues. Stability data are usually generated under defined accelerated conditions and then extrapolated with stated assumptions.
Lyophilized material is generally held at -20 degrees Celsius or lower, desiccated and protected from light, where it remains stable for extended periods. Reconstituted or ready-to-use solution is usually kept at 2 to 8 degrees Celsius with minimal agitation. Repeated freeze-thaw cycles should be avoided because they promote aggregation and reduce the soluble monomer fraction. Shipment of frozen solid commonly uses dry ice, while refrigerated liquid moves with validated cold packs. Stability beyond documented periods is not established.
Characterization of the peptide relies on reversed-phase high-performance liquid chromatography for purity and related-substance profiling, with ultraviolet detection near 214 nanometers. Mass spectrometry confirms molecular mass and reveals modifications such as oxidation or deamidation. Peptide mapping after enzymatic digestion verifies the amino acid sequence, while amino acid analysis supplies compositional data. Circular dichroism and infrared spectroscopy are used to assess secondary structure, particularly the alpha-helical content that influences aggregation behavior in solution.
Common degradation routes include hydrolysis of labile amide bonds, deamidation of asparagine and glutamine residues, oxidation of methionine and tryptophan, and non-covalent aggregation. Aggregates can form during freeze-thaw cycling, at elevated pH, or when peptide concentration is high. Each route produces characteristic chromatographic or mass shifts that are tracked during stability studies. Whether a given minor impurity alters biological activity is often an open question, and specification limits are typically set on identity and purity rather than on functional data for trace species.
The cultivation of plants from which psychotropic substances are obtained is not controlled by the Vienna Convention... Neither the crown (fruit, mescal button) of the Peyote cactus nor the roots of the plant Mimosa hostilis nor Psilocybe mushrooms themselves are included in Schedule I, but only their respective principals, mescaline, DMT, and psilocin. In Peru, ayahuasca is legal and formally protected as part of the country's cultural heritage. When ratifying the 1971 Convention on Psychotropic Substances, Peru entered a reservation to exclude Ayahuasca and San Pedro from international control, citing their traditional ritual use by Amazonian peoples (United Nations Treaty Collection, 1971). This position was reinforced on 24 June 2008, when the Instituto Nacional de Cultura declared the traditional knowledge and ceremonial use of Ayahuasca by Indigenous communities as Patrimonio Cultural de la Nación (Cultural Heritage of the Nation). A fax from the Secretary of the International Narcotics Control Board (INCB) to the Netherlands Ministry of Public Health sent in 2001 goes on to state that "Consequently, preparations (e.g. decoctions) made of these plants, including ayahuasca, are not under international control and, therefore, not subject to any of the articles of the 1971 Convention." Despite the INCB's 2001 affirmation that ayahuasca is not subject to drug control by international convention, in its 2010 Annual Report the Board recommended that governments consider controlling (i.e. criminalizing) ayahuasca at the national level.
== Research == As of 2025, the department has 162 researchers, including 110 post-graduate researchers, 50 postdoctoral researchers and 49 research groups. Research spans four divisions including cellular and molecular pathology, immunology, microbiology and parasitology and virology.
Also in 1893, Édouard Laguesse suggested that the islet cells of the pancreas, described as "little heaps of cells" by Paul Langerhans in 1869, might play a regulatory role in digestion. These cells were named Islets of Langerhans after the original discoverer. Soon after, it was established that the role of the pancreas in carbohydrate metabolism could be localized to the islets; Eugene Lindsay Opie (1901) confirmed this connection in relation to diabetes mellitus. In 1909, Belgian physician Jean de Mayer hypothesized that the islets secrete a substance that plays this metabolic role, and termed it insulin, from the Latin insula ('island'). Sir Edward Albert Sharpey-Schafer independently proposed the same in 1916, not knowing at the time that de Meyer had made the same suggestion a few years prior. The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was further clarified between 1921 and 1922 when a group of researchers in Toronto, including Frederick Banting, Charles Best, John MacLeod, and James Collip, were able to isolate and purify the extract.
The Na+/I− symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodide ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient. This is called iodide trapping. Sodium is cotransported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. I− is moved across the apical membrane into the colloid of the follicle by pendrin. Hydrogen peroxide is also introduced into the follicle by the action of DUX (Dual Oxidase). Iodide is non-reactive, and the reactive I2 species is required for the next step. Thyroid peroxidase (TPO) reduces hydrogen peroxide to water by transferring one electron from two I− atoms that react to form I2. Iodine (I2) is converted into HOI, by hydration with water. Both I2 and HOI iodinate specific tyrosyl residues of the thyroglobulin within the colloid to form 3-monoiodityrosyl (MIT-yl) and 3,5-diiodityrosyl (DIT-yl) residues—introducting iodine atoms at one or both locations ortho to the hydroxyls of tyrosine. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid. TPO also converts tyrosyl, MIT-yl, and DIT-yl residues into their free radical forms. These forms attack other MIT-yl and DIT-yl residues. When a DIT-yl radical attacks a DIT, T4-yl (peptidic T4) is formed. When a MIT-yl radical attacks a DIT, T3-yl is formed.
==== Elimination ==== Minoxidil is excreted almost exclusively (>97%) in urine. About 10 to 15% is excreted in urine unchanged. The elimination half-life of oral minoxidil is about 3 to 4 hours. Conversely, the half-life of topical minoxidil is 22 hours on average. Oral minoxidil is excreted within 12 to 20 hours in urine. Despite this however, the hypotensive effect of oral minoxidil lasts approximately 72 hours following a single dose. With discontinuation of topical minoxidil, about 95% of systemically absorbed minoxidil is excreted within 4 days. The renal clearance of oral minoxidil is 352 mL/minute.
Sources: en.wikipedia.org
=== Malay === Malay, just like Indonesian, is an agglutinative language (at least in the formal language) and it belongs to the Austronesian language family. The longest word in Malay is mempertanggungjawabkan, which is 22 letters long, meaning "to give responsibility to" in English.
Fake-fiction is a genre that deliberately presents real, unscripted events in the form of a fiction film, making them appear staged. The concept was introduced by Pierre Bismuth to describe his 2016 film Where is Rocky II?
Theanine , also known as L-γ-glutamylethylamide, N5-ethyl-L-glutamine, or γ-glutamylethylamide, is a bioactive, non-proteinogenic amino acid similar to the proteinogenic amino acids glutamic acid and L-glutamine. It is produced by certain plants such as the tea plant (Camellia sinensis), and by some fungi. Theanine was discovered in 1949 as a constituent of green tea and was isolated in 1950 from gyokuro tea leaves. Theanine constitutes about 1–2% of the dry weight of green tea leaves. Theanine is sold as a dietary supplement. It is packaged in gelatin capsules, tablets, and as a powder, and may be an ingredient in branded supplements with caffeine. It is also used as an ingredient in food and beverages. Japan approved its unlimited use in all foods (including chocolates, soft drinks, and herb teas) except infant food in 1964, and the US Food and Drug Administration has considered it safe at doses up to 250 milligrams (mg) per serving since 2007. In 2011, the European Food Safety Authority found there was insufficient evidence for a causal relationship between theanine consumption and improved cognitive function, alleviation of psychological stress, maintenance of normal sleep, or reduction of menstrual discomfort. A 2025 review found that theanine has been poorly studied to date, having inconsistent research quality and unreliable clinical trials.
0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no proteinuria 1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage 2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage 3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2 4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2 5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis. Note: others add a "T" to patients who have had a transplant regardless of stage. Not all clinicians agree with the above classification, suggesting that it may mislabel patients with mildly reduced kidney function, especially the elderly, as having a disease. A conference was held in 2009 regarding these controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on CKD: Definition, Classification and Prognosis, gathering data on CKD prognosis to refine the definition and staging of CKD.
=== By Palestinian militants === The IDF has accused Hamas of using child soldiers and of positioning children on the front lines. Israeli officials claim Hamas and Islamic Jihad had for years run summer camps in the Gaza Strip where children underwent military training. According to the Coordinator of Government Activities in the Territories, a unit of the Israeli Ministry of Defense, "a senior Hamas militant" said Hamas used children to transport explosives. Israel also claims Hamas sent over one hundred children and women to a compound the IDF was targeting to act as human shield in November 2023, that they had found entrances to multiple Hamas tunnels near and under children's beds during the war, and that children are used by Hamas to scout and observe the IDF forces, reporting activity, locations, and extent of the forces. Neve Gordon, professor of international law and human rights and co-author of the 2020 book Human Shields: A History of People in the Line of Fire, has stated that Israeli military and government claims of Hamas using Palestinian civilians as human shields "should be understood as a pre-emptive legal defence against accusations that Israel is committing war crimes and crimes against humanity in Gaza". Janina Dill, a laws of war professor at University of Oxford, stated, "Even if Hamas uses civilians as human shields, those civilians are entitled to full protection under international law unless they directly participate in the fighting".
Sources: en.wikipedia.org
It is a synthetic 39-amino-acid peptide that acts on two incretin receptors, the GIP receptor and the GLP-1 receptor. It is given by subcutaneous injection and has a circulating half-life of roughly five days. It is not a small molecule and is not absorbed usefully from the gut in conventional oral form.
Selective agents act on one receptor, while tirzepatide engages both GIP and GLP-1 receptors. The added GIP activity may contribute effects on insulin sensitivity and on fat metabolism. Whether the dual action produces meaningful clinical advantages beyond differences in potency is still being examined.
The downstream consequences of GIP receptor activation are not fully characterised in humans. It is also unclear how much each receptor contributes to appetite reduction and to shifts in body composition. Published work describes associations and proposed pathways rather than settled causal chains.
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。