dual agonist comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2026-07-20. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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。
纯度评估通常综合反相色谱、体积排阻色谱与质谱三方面信息：前者反映疏水性杂质，后者反映聚集体，质谱则确认分子量与主要降解产物。有关降解途径的完整图谱——例如脱酰胺、氧化与水解各占多大比例——在不同储存条件下仍有差异，属于需要逐案验证的问题。
| 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 |
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.
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.
Structural work on the molecule centers on a C20 fatty diacid moiety attached through a linker to the peptide backbone. This side chain promotes reversible binding to serum albumin, which slows renal clearance and supports a prolonged action profile. The peptide backbone incorporates aminoisobutyric acid substitutions that limit recognition by digestive enzymes. Together these modifications produce a molecule that is stable enough for subcutaneous delivery but still dependent on careful manufacturing control. Analytical characterization of the active pharmaceutical ingredient typically follows the conventions used for other synthetic peptides.
Tirzepatide is a synthetic peptide composed of 39 amino acids. It acts as a dual agonist at two incretin receptors, the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. The molecule was designed by modifying the native sequence of glucose-dependent insulinotropic polypeptide to improve metabolic stability and extend its circulation time. Its structure includes several non-natural amino acid residues and a fatty acid side chain. These features distinguish it from earlier single-receptor incretin analogs studied in the same period.
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.
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.
=== Commonly used inbred strains === There are many strains of mice used in research, however, inbred strains are usually the animals of choice for most fields. Inbred mice are defined as being the product of at least 20 generations of brother X sister mating, with all individuals being derived from a single breeding pair. Inbred mice have several traits that make them ideal for research purposes. They are isogenic, meaning that all animals are nearly genetically identical. Approximately 98.7% of the genetic loci in the genome are homozygous, so there are probably no "hidden" recessive traits that could cause problems. They also have very unified phenotypes due to this stability. Many inbred strains have well documented traits that make them ideal for specific types of research. The following table shows the top 10 most popular strains according to Jackson Laboratories.
In 1959, Nikita Khrushchev launched an anti-religious campaign. Of the 50 churches that were operating in Moscow in 1959, 30 were closed and six demolished. On 8 May 1965, the 20th anniversary of the Soviet victory in World War II, Moscow was awarded the honorary title of Hero City. The Moscow Ring Road (MKAD) was opened in 1961. It had four lanes running 109 kilometers (68 mi) along city borders. The MKAD marked the administrative boundaries of the city until the 1980s, when outlying suburbs beyond the ring road were incorporated. In 1980, Moscow hosted the Summer Olympic Games, which were boycotted by the United States and other Western countries because the Soviet Union invaded Afghanistan in 1979. In 1991, Moscow was the scene of a coup attempt by conservative communists opposed to the liberal reforms of Mikhail Gorbachev.
=== Pharmaceutical excipients === Some pharmaceutical products require protection from oxidation. A number of antioxidants can be used as excipients. Sequestrants such as disodium EDTA can also be used to prevent metal-catalyzed oxidation.
=== Animal-derived === Some drugs used in modern medicine have been discovered in animals or are based on compounds found in animals. For example, the anticoagulant drugs, hirudin and its synthetic congener, bivalirudin, are based on saliva chemistry of the leech, Hirudo medicinalis. Used to treat type 2 diabetes, exenatide was developed from saliva compounds of the Gila monster, a venomous lizard.
== Background == The monoisotopic mass is not used frequently in fields outside of mass spectrometry because other fields cannot distinguish molecules of different isotopic composition. For this reason, mostly the average molecular mass or even more commonly the molar mass is used. For most purposes such as weighing out bulk chemicals only the molar mass is relevant since what one is weighing is a statistical distribution of varying isotopic compositions. This concept is most helpful in mass spectrometry because individual molecules (or atoms, as in ICP-MS) are measured, and not their statistical average as a whole. Since mass spectrometry is often used for quantifying trace-level compounds, maximizing the sensitivity of the analysis is usually desired. By choosing to look for the most abundant isotopic version of a molecule, the analysis is likely to be most sensitive, which enables even smaller amounts of the target compounds to be quantified. Therefore, the concept is very useful to analysts looking for trace-level residues of organic molecules, such as pesticide residue in foods and agricultural products. Isotopic masses can play an important role in physics, but physics less often deals with molecules. Molecules differing by an isotope are sometimes distinguished from one another in molecular spectroscopy or related fields; however, it is usually a single isotope change on a larger molecule that can be observed rather than the isotopic composition of an entire molecule.
Sources: en.wikipedia.org
== See also == Black box Bus analyzer Computer data logging: logging APIs, server logs & syslog, web logging & web counters Continuous emissions monitoring system Runtime intelligence Sequence of events recorder SensorML Shock and vibration data logger Temperature data logger
=== Passion fruit === The term "passion fruit" in English comes from the passion flower, as an English translation of the Latin genus name, Passiflora, and may be spelled "passion fruit", "passionfruit", or "passion-fruit". Around 1700, the name Passiflora was given by missionaries in Brazil as an educational aid to convert the Indigenous inhabitants to Christianity: its name was flor das cinco chagas or "flower of the Five Wounds" to illustrate the crucifixion of Christ and his resurrection, with other plant components also named after instruments of the Passion of Jesus.
== History == In 1908, what appears to be the first case of Urbach–Wiethe disease was reported by Friedrich Siebenmann, a professor of otolaryngology in Basel, Switzerland. In 1925, Friedrich Miescher, a Swiss dermatologist, reported on three similar patients. An official report of Urbach–Wiethe disease was first described in 1929 by a Viennese dermatologist and otorhinolaryngologist, Urbach and Wiethe. Its original name of 'lipoidosis cutis et mucosae' was changed to 'lipoid proteinosis cutis et mucosae' due to Urbach's belief that the condition was due to abnormal lipid and protein deposits within the tissues. Some have debated as to whether or not the disease is actually a form of mucopolysaccharidosis, amyloidosis, or even porphyria. The discovery of the Urbach–Wiethe disease causing mutation to the ECM1 gene has now provided a definitive way to differentiate Urbach–Wiethe disease from these other conditions. A woman with Urbach–Wiethe disease, S.M., was a woman unable to feel fear. She has been extensively studied, which helped determine the function of the amygdala.
Acheson SA, Kirkman HN, Wolfenden R (1988). "Equilibrium of 5,6-hydration of NADH and mechanism of ATP-dependent dehydration". Biochemistry. 27 (19): 7371–5. doi:10.1021/bi00419a030. PMID 3061454. MEINHART JO, CHAYKIN S, KREBS EG (1956). "Enzymatic conversion of a reduced diphosphopyridine nucleotide derivative to reduced diphosphopyridine nucleotide". J. Biol. Chem. 220 (2): 821–9. doi:10.1016/S0021-9258(18)65307-4. PMID 13331940. Regueiro V, Campos MA, Pons J, Alberti S, Bengoechea JA (2006). "The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells". Microbiology. 152 (Pt 2): 555–66. doi:10.1099/mic.0.28285-0. PMID 16436443.
Sources: en.wikipedia.org
Christopher Layne claims that the preponderance of power has been the dominant US strategy during both the Cold War and the post-Cold War periods. "Preponderance's strategic imperatives are the same as they were during the post-World War II era: pacification and reassurance in Europe and East Asia, and protection of these regions from instability in the periphery." The post-Cold War strategy of preponderance holds that "only a preponderance of US power ensures peace" which is "the result of an imbalance of power in which US capabilities are sufficient, operating on their own, to cow all potential challengers and to comfort all coalition partners. It is not enough consequently to be primus inter pares [...] One must be primus solus." Layne since the beginning of the post-Cold war period expects the preponderance of power to trigger counterbalancing. He finds that "it was the bipolar structure of the postwar system that allowed Washington to pursue a strategy of preponderance successfully" and thereby smother the emergence of other great powers. But the preponderance of power which "others found merely irritating in a bipolar world may seem quite threatening in a unipolar world." Because of these structural factors, "an American strategy of preponderance [...] is doomed to failure"; it will "cause other states to balance against the United States". Overturning the scholarly conventional wisdom, however, the current preponderant power seems to render inoperative the counterbalancing long central to research in international relations.
The first launch of a cruise missile (SSM-N-8 Regulus) from a submarine occurred in July 1953, from the deck of USS Tunny, a World War II fleet boat modified to carry the missile with a nuclear warhead. Tunny and its sister boat, Barbero, were the United States' first nuclear deterrent patrol submarines. In the 1950s, nuclear power partially replaced diesel–electric propulsion. Equipment was also developed to extract oxygen from sea water. These two innovations gave submarines the ability to remain submerged for weeks or months. Most of the naval submarines built since that time in the US, the Soviet Union (now Russia), the UK, and France have been powered by a nuclear reactor. In 1959–1960, the first ballistic missile submarines were put into service by both the United States (George Washington class) and the Soviet Union (Golf class) as part of the Cold War nuclear deterrent strategy. During the Cold War, the US and the Soviet Union maintained large submarine fleets that engaged in cat-and-mouse games. The Soviet Union lost at least four submarines during this period: K-129 was lost in 1968 (a part of which the CIA retrieved from the ocean floor with the Howard Hughes-designed ship Glomar Explorer), K-8 in 1970, K-219 in 1986, and Komsomolets in 1989 (which held a depth record among military submarines—1,000 m (3,300 ft)). Many other Soviet subs, such as K-19 (the first Soviet nuclear submarine, and the first Soviet sub to reach the North Pole) were badly damaged by fire or radiation leaks.
As with other hormones, hGH levels often decline with age, but this decrease is not necessarily bad. At least one epidemiological study suggests that people who have high levels of hGH are more apt to die at younger ages than those with lower levels of the hormone. Researchers have also studied animals with genetic disorders that suppress growth hormone production and secretion and found reduced growth hormone secretion may actually promote longevity in those species that have been tested. The Clinical Interventions in Aging review also stated that although the decreasing levels of the hormone seen in the elderly might reduce quality of life, this change could protect from age-related diseases and cited evidence linking GH to cancer. This concern was mirrored in a 2008 review published in Clinical Endocrinology, which stated that the risk of increasing the incidence of cancer was a strong argument against the use of this hormone as an "elixir of youth" in healthy adults.
Samples for dating need to be converted into a form suitable for measuring the 14C content; this can mean conversion to gaseous, liquid, or solid form, depending on the measurement technique to be used. Before this can be done, the sample must be treated to remove any contamination and any unwanted constituents. This includes removing visible contaminants, such as rootlets that may have penetrated the sample since its burial. Alkali and acid washes can be used to remove humic acid and carbonate contamination, but care has to be taken to avoid removing the part of the sample that contains the carbon to be tested.
Enavogliflozin (DWP16001/GCC5694A) is a selective SLC5A2 and SGLT2 inhibitor developed to treat diabetes and obesity. It was developed by GC Pharma and Daewoong Pharmaceutical. Enavogliflozin has been approved for clinical use in South Korea, and Ecuador, and applied for approval in Brazil, Mexico, Peru, and Colombia. In a meta-analysis published by Dutta et al. analysing data from 4 trials over 6 months of clinical use, enavogliflozin was well tolerated and was found to be effective for managing type 2 diabetes and may be superior to dapagliflozin with regard to certain clinical aspects
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.
建议在低温、避光、干燥环境中密封保存，常见条件为 2 至 8 摄氏度，长期存放可置于更低温度。应避免反复冻融，并尽量减少容器开启次数。