The short version of Dual agonist fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-12-06 and is reviewed periodically as new material appears.
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.
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 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 |
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.
The peptide activates two G protein-coupled receptors, GIPR and GLP-1R. Binding triggers adenylyl cyclase activity and raises intracellular cyclic AMP in pancreatic beta cells, which potentiates insulin release when glucose is elevated. Signaling in the central nervous system is associated with reduced appetite and lower energy intake, while effects on gastric emptying and glucagon secretion are also reported. Because activity at both receptors is retained, the pharmacological profile is often described as incretin-based rather than selective for a single receptor.
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.
Tirzepatide is a synthetic peptide built from thirty-nine amino acids. Its sequence is derived from native glucose-dependent insulinotropic polypeptide, or GIP, with several non-natural residues and a fatty diacid side chain attached through a linker. The molecule behaves as a dual agonist at two incretin receptors, GIP and GLP-1, instead of targeting a single receptor. This dual engagement separates it from earlier single-receptor incretin compounds and underpins most of its reported pharmacological activity.
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.
==== Other ==== The use of statins in diabetes to prevent cardiovascular disease should be considered after evaluating the person's total risk for cardiovascular disease. The use of aspirin (acetylsalicylic acid) to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended in people with previous cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. Aspirin as primary prevention may have greater risk than benefit, but could be considered in people aged 50 to 70 with another significant cardiovascular risk factor and low risk of bleeding after information about possible risks and benefits as part of shared-decision making. Vitamin D supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c. Sharing their electronic health records with people who have type 2 diabetes helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.
=== Peru === Joseph Dombey, in a letter written from Lima on 20 May 1779, specifies the ancestral way used by the Peruvians to prepare potatoes that constitute, along with maize (U.S.: "corn"), their primary foods. Further, that they carry potatoes in haversacks on long journeys, for which the potato is prepared by cooking it in water, then peeling it, and finally exposing it to the wind and sun until it has completely dried. The process can preserve it "several centuries, by guaranteeing it of the humidity". This papa seca (dried potato) is then mixed in with other foods to make meals. Another process consists of freezing the potato and treading on it to remove the skin. Thus prepared, it is put in running water and loaded with stones. Fifteen or twenty days later, it is exposed to the sun until it dries. It becomes the chuño, "a real starch, with which one could make powder for the hair". The Peruvians use it to prepare jams, a flour for convalescents, and mix it with almost all their dishes. An author of the 20th century points out that the process of the Peruvians, who operate by freezing followed by dehydration, is none other than "a freeze-drying by the natural means". He specifies that the tubers are left in frozen water several nights before being exposed to the sun and trodden on and that, "to make the product suitable for consumption, it is enough to put it back in water". According to him, the Spaniards used this preparation in the 16th century to feed the indigenous people forced to work in the silver mines of Potosi.
He will be strong enough to get up and two days later he leaves the home.However, even in 1934 he was suspicious of the idea that the treatment was pure conditioned reflex – "though vomiting is one of the ways that apomorphine relives the patient, I do not believe it to be its main therapeutic effect." – and by 1948 he wrote:It is now twenty-five years since I began treating cases of anxiety and alcoholism with apomorphine, and I read my first paper before this Society fourteen years ago. Up till then I had thought, and, unfortunately, I said in my paper, that the virtue of the treatment lay in the conditioned reflex of aversion produced in the patient. This statement is not even a half truth… I have been forced to the conclusion that apomorphine has some further action than the production of a vomit.This led to his development of lower-dose and non-aversive methods, which would inspire a positive trial of his method in Switzerland by Dr Harry Feldmann.
=== Overexpression in cancers === CUX1 is overexpressed in many cancers. The comprehensive molecular characterization of human colon and rectal cancer performed by The Cancer Genome Atlas (TCGA) ranked CUX1 as the fifth gene on a scale showing a correlation between tumour aggressiveness and gene expression/somatic copy number alterations. TCGA and REMBRANDT data also show shorter survival of glioblastoma patients with high CUX1 mRNA expression (reviewed). In smaller scale studies, immunohistochemical analyses on breast, pancreas and glioblastoma cancers reveal that CUX1 expression inversely correlates with relapse-free and overall survival. An alternative CUX1 transcript that is initiated within intron 20 and codes for a p75 isoform is expressed specifically in the testis and thymus. This transcript was found to be aberrantly expressed in many breast tumour cells lines and breast tumours. Transgenic mice expressing this transcript in mammary epithelial cells were shown to develop mammary tumours with metastasis to the lung.
deliquescence A substance's affinity for water, often characterized as its tendency to absorb moisture from the atmosphere to form aqueous solutions. Most strongly deliquescent substances are salts, such as calcium chloride and potassium carbonate.
Sources: en.wikipedia.org
== See also == List of University of California, Berkeley faculty List of University of California, Berkeley alumni in business and entrepreneurship List of University of California, Berkeley alumni in science and technology
== See also == Madrigal v. Quilligan No más bebés Sterilization law in the United States Eugenics in the United States Sterilization of Native American women Compulsory sterilization Anti-Mexican sentiment Chicano Movement Abortion rights movements East L.A. Walkouts Women's Rights
== Dye colour == The suffix "R" in the name of Coomassie brilliant blue R-250 is an abbreviation for "red" as the blue colour of the dye has a slight reddish tint. For the "G" variant the blue colour has a more greenish tint. The "250" originally denoted the purity of the dye. The colour of the two dyes depends on the acidity of the solution. The "G" form of the dye has been studied in detail. At a pH of less than 0 the dye has a red colour with an absorption maximum at a wavelength of 465 nm. At a pH of around 1 the dye is green with an absorption maximum at 620 nm while above pH 2 the dye is bright blue with a maximum at 595 nm. At pH 7 the dye has an extinction coefficient of 43,000 M−1 cm−1. The different colours are a result of the different charged states of the dye molecule. In the red form, all three nitrogen atoms carry a positive charge. The two sulfonic acid groups have extremely low pKa and will normally be negatively charged, thus at a pH of around zero the dye will be a cation with an overall charge of +1. The green colour corresponds to a form of the dye with no net overall charge. In neutral media (pH 7), only the nitrogen atom of the diphenylamine moiety carries a positive charge and the blue dye molecule is an anion with an overall charge of −1. The pKa values for the losses of the two protons are 1.15 and 1.82, respectively. The final proton is lost under alkaline conditions and the dye becomes pink (pKa 12.4). The dye interacts electrostatically but noncovalently with the amino and carboxyl groups of proteins.
Temperature swing solvent extraction is an experimental technique for the desalination of drinking water. It has been used to remove up to 98.5% of the salt content in water, and is able to process hypersaline brines that cannot be desalinated using reverse osmosis.
=== 1990 === 5 August The Nuts and Bolts of Ben Bowlby, 23 year old Ben Bowlby; his sister Sophie studied costume design; his father was a photographer at the Royal Free Hospital; the first fifteen minutes would be shown as part of the November 1991 episode; monocoque structures; his child psychiatrist grandfather John Bowlby, the son of Sir Anthony Bowlby; Frank Dernie at Team Lotus in Norfolk, and automotive diffusers; circuits at Snetterton Circuit. Narrated by Martin Jarvis, directed by Patrick Uden, made by Uden Associates 12 August The Greenhouse Conspiracy 19 August Selling the Secret, about the Soviet Union selling technology; it visited the Khrunichev State Research and Production Space Center in Moscow. Produced by Paul Murricane, directed by Ross Wilson, made by Scottish Television 2 September Blue Skies, about British innovation and its funding; biologist Nigel R.
Sources: en.wikipedia.org
Straight-chain alkanes are sometimes indicated by the prefix n- (for "normal") where a non-linear isomer exists. Although this is not strictly necessary and is not part of the IUPAC naming system, the usage is still common in cases where one wishes to emphasize or distinguish between the straight-chain and branched-chain isomers, e.g., "n-butane" rather than simply "butane" to differentiate it from isobutane. Alternative names for this group used in the petroleum industry are linear paraffins or n-paraffins. The first eight members of the series (in terms of number of carbon atoms) are named as follows:
== Communication == The nearest Airport is Bhubaneswar & Railway Station is Bhadrak (Charampa). The distance from Bhadrak is 80 km by road and about 220 km. from Bhubaneswar, the state capital of Odisha.
Human-animal chimeras include humans having undergone non-human to human xenotransplantation, which is the transplantation of living cells, tissues or organs from one species to another. Patient derived xenografts are created by xenotransplantation of human tumor cells into immunocompromised mice, and is a research technique frequently used in pre-clinical oncology research.
The subject was said to have “agrypnia excitata”, which consists of severe total insomnia of long duration associated with decreased vigilance, mental confusion, hallucinations, motor agitation, and complex motor behavior mimicking dreams, and autonomic activation. CNS and autonomic symptoms were caused by impaired corticolimbic control of the subcortical structures regulating the sleep-wake and autonomic functions.
=== Hydrogen bonding and solubility === Because of the greater electronegativity of oxygen than nitrogen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. In primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen atom can accept hydrogen bonds from water and the N–H hydrogen atoms can donate H-bonds. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons. These hydrogen bonds also have an important role in the secondary structure of proteins. The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water.
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.
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。