The short version of circular dichroism fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-07-06. 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.
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.
Identity and purity are usually established with reversed-phase high-performance liquid chromatography for the main peak and with mass spectrometry for the observed molecular mass. Peptide mapping after enzymatic digestion confirms the primary sequence, while amino acid analysis provides a quantitative composition check. Size-exclusion chromatography and ion-exchange chromatography are used to look for aggregates and charge variants. Water content, residual solvents, and counter-ion content are measured separately, since a lyophilised powder is often reported on an as-is basis unless a correction is applied.
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.
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.
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.
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.
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.
Tirzepatide is a synthetic peptide built from 39 amino acid residues. Its sequence is related to human glucose-dependent insulinotropic polypeptide, with modifications that include a C-terminal extension and a C20 fatty diacid joined through a linker. Those changes raise the molecule's affinity for serum albumin, which slows renal filtration and lengthens the time it stays in circulation. The free base has an average molecular mass near 4813.5 daltons. The compound is made by solid-phase peptide synthesis followed by chromatographic purification.
SPB Hospitality is a multi-brand restaurant operator headquartered in Houston, Texas. The company owns several casual dining restaurant chain brands, including Logan's Roadhouse, Old Chicago Pizza + Taproom, J. Alexander's, Stoney River Legendary Steaks, Krystal Restaurants, Gordon Biersch Brewery Restaurants, and Rock Bottom Restaurants Breweries. It is the owner of the holdings of the former CraftWorks Company. As of November 2019, CraftWorks owned and operated over 390 restaurants in the United States, but all of its owned-and-operated locations closed by March 2020, after a Chapter 11 bankruptcy followed immediately by the COVID-19 pandemic in the United States, and CraftWorks terminated its 18,000 employees, leaving fewer than 25 employed. On June 12, 2020, SPB Hospitality purchased Craftworks businesses out of bankruptcy for $93 million.
The Gβγ subunit is essential for the formation of heterotrimeric G protein through its association with the Gα subunit allowing the G proteins coupling to the GPCR. Therefore, any agent inhibiting the Gβγ subunits signalling effects must not interfere with the heterotrimeric G protein formation or Gα subunit signalling. Gβγ expression is universal throughout almost all the cells of the body so any agent acting to inhibit this subunit could elicit numerous side effects. Small molecule inhibitors that target the coupling of Gβγ to specific effectors and do not interfere with normal G protein cycling/ heterotrimeric formation, have the potential to work as therapeutic agents in treating some specific diseases.
=== 2009–2013: Time Machine Tour and Clockwork Angels === On February 16, 2009, Lifeson remarked that the band might begin working on a new album in the fall of 2009, with Nick Raskulinecz again producing. In November 2009, Lee, Lifeson and Peart were awarded the International Achievement Award at the annual SOCAN Awards in Toronto. On March 19, 2010, the CBC posted a video interview with Lee and Lifeson in which they discussed Rush's induction into the Canadian Songwriters Hall of Fame on March 28, 2010, at the Toronto Centre for the Arts' George Weston Recital Hall. The band was recognized for the songs "Limelight", "Closer to the Heart", "The Spirit of Radio", "Tom Sawyer" and "Subdivisions". In addition to discussing their induction, Lee and Lifeson touched on future material, with Lee saying, "Just about a month and a half ago we had no songs. And now we've been writing, and now we've got about 6 songs that we just love..." On March 26, 2010, in an interview with The Globe and Mail, Lifeson remarked that there was even the potential for two supporting tours. Soon afterwards, Peart confirmed that Raskulinecz had returned as co-producer. In April 2010, Rush recorded "Caravan" and "BU2B", two new songs to be featured on the band's then-upcoming studio album Clockwork Angels, at Blackbird Studios in Nashville with Raskulinecz. "Caravan" and "BU2B" were released together on June 1, 2010, and made available for digital download.
=== E3-Deficient === This type of MSUD is diagnosed from the deficiencies of the E3 subunit. Variants in the E3 subunit tend to cause more severe symptoms than other subunit variants, and can cause cause congenital lactic acidosis that is termed DLD deficiency. There may be varying level of enzyme activity.
Bronchial circulation In the bronchial circulation that supplies blood to the lung tissues, bronchial veins drain venous blood from the large main bronchi into the azygous vein, and ultimately the right atrium. Venous blood from the bronchi inside the lungs drains into the pulmonary veins and empties into the left atrium; since this blood never went through a capillary bed it was never oxygenated and so provides a small amount of shunted deoxygenated blood into the systemic circulation.
Sources: en.wikipedia.org
Journal of Clinical Investigation (Papers Presented / Proceedings of the Fifty-Fourth Annual Meeting of the American Society for Clinical Investigation, April 30, 1962. 41 (6): 1340. Daly, M.M.; Deming, Q.B.; Raeff, V.M.; Brun, L.M. (October 1963). "Cholesterol Concentration and Cholesterol Synthesis in Aortas of Rats With Renal Hypertension" (PDF). Journal of Clinical Investigation. 42 (10): 1606–1612. doi:10.1172/JCI104845. PMC 289439. PMID 14074354. Adel, H.N.; Deming, Q.B.; Daly, M.M.; Raeff, V.M.; Brun, L.M. (October 1965). "The Effect of Experimental Hypertension on Cholesterol Synthesis in the Rat". Journal of Clinical and Laboratory Medicine. 66 (4): 571–581. PMID 5843085. Wolinsky, Harvey; Daly, Marie M. (November 1970). "A Method for the Isolation of Intima-Media Samples from Arteries". Proceedings of the Society for Experimental Biology and Medicine. 135 (2): 364–368. doi:10.3181/00379727-135-35052. PMID 4921030. S2CID 46610507. Daly, M.M. (May 1971). "Biosynthesis of squalene and sterols by rat aorta". Journal of Lipid Research. 12 (3): 367–375. doi:10.1016/S0022-2275(20)39518-3. PMID 5579265. Daly, Marie M. (September 1972). "Effects of Hypertension on the Lipid Composition of Rat Aortic Intima-Media". Circulation Research. 31 (3): 410–416. doi:10.1161/01.res.31.3.410. PMID 5057020. S2CID 12008214. Wolinsky, Harvey; Goldfischer, Sidney; Daly, Marie M.; Kasak, Lisa E.; Coltoff-Schiller, Bernice (April 1975). "Arterial Lysosomes and Connective Tissue in Primate Atherosclerosis and Hypertension". Circulation Research. 36 (4): 553–561. doi:10.1161/01.res.36.4.553.
The vast majority of plants are C3, meaning they photorespire when necessary. Certain species of plants or algae have mechanisms to lower the uptake of molecular oxygen by RuBisCO. These are commonly referred to as Carbon Concentrating Mechanisms (CCMs), as they increase the concentration of CO2 so that RuBisCO is less likely to produce glycolate through reaction with O2.
Ejaculation is the ejection of semen from the penis. It is usually accompanied by orgasm. A series of muscular contractions delivers semen, containing male gametes known as sperm cells or spermatozoa, from the penis. Ejaculation usually happens as the result of sexual stimulation, but it can be due to prostatic disease in rare cases. Ejaculation may occur spontaneously during sleep (known as a nocturnal emission). Anejaculation is the condition of being unable to ejaculate. Sperm are produced in the testicles and stored in the attached epididymides. During ejaculation, sperm are propelled up the vasa deferentia, two ducts that pass over and behind the bladder. Fluids are added by the seminal vesicles and the vasa deferentia turn into the ejaculatory ducts, which join the urethra inside the prostate. The prostate, as well as the bulbourethral glands, add further secretions (including pre-ejaculate), and the semen is expelled through the penis. Ejaculation has two phases: emission and ejaculation proper. The emission phase of the ejaculatory reflex is under control of the sympathetic nervous system, while the ejaculatory phase is under control of a spinal reflex at the level of the spinal nerves S2–4 via the pudendal nerve. A refractory period succeeds the ejaculation, and sexual stimulation precedes it. The ischiocavernosus muscle helps to stabilize the penis during erection by compressing the crus and slowing the return of blood through the veins. The bulbospongiosus muscle also contributes to erection along with the expulsion of urine and semen.
=== March === 1 March – 2024 Rochdale by-election: Sir Keir Starmer apologises to the voters of Rochdale for disowning the Labour Party's candidate, but says it was "the right decision". In a statement outside 10 Downing Street, Sunak warns that Islamists and far-right extremists, which he describes as "two sides of the same extremist coin", are trying to "deliberately" undermine the UK's "multi-faith democracy", and says the UK must face them down. Figures from the National Audit Office show the UK government will pay Rwanda a total of £350m for the agreement to take asylum seekers, with £150,000 also being paid to Rwanda for each person sent there. Conservative peer Lord Bamford, chairman of JCB, retires from the House of Lords. 2–3 March – The London Labour conference is held at the Leonardo Royal Hotel in Tower Bridge. 4 March – Sunak says the UK economy is "getting on the right track" ahead of what is expected to be the last budget before the next election. George Galloway is sworn in as an MP at Westminster. Paul Scully, MP for Sutton and Cheam, announces he is standing down from Parliament at the next general election. Lee Waters announces he is stepping down as Wales's Transport Minister when the new First Minister of Wales is elected. 5 March – A bid by the Welsh Conservatives and Welsh Liberal Democrats to change planned reforms to the way Senedd members are elected from the 2026 election is rejected by the parliament. 6 March – Chancellor Jeremy Hunt delivers the 2024 United Kingdom budget.
Fatty change, or steatosis, is the accumulation of fatty acids in liver cells. This can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macro-vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into carbon dioxide (CO2) and water (H2O). This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver.
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。