If you have been reading about 有关物质 and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2026-01-01. Numbers and descriptions here follow the published literature rather than marketing material.
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.
Development of tirzepatide took place under a research program that sought to test whether simultaneous engagement of two incretin receptors would produce greater metabolic effects than single-receptor agonism. Clinical trials were organized into the SURPASS series for type 2 diabetes and the SURMOUNT series for obesity and weight management. Regulatory clearance for type 2 diabetes came in 2022 in the United States, followed by approval for chronic weight management in 2023. The trial programs reported reductions in glycated hemoglobin and body weight relative to comparators, though long-term cardiovascular and durability data continue to accumulate.
The peptide backbone contains 39 amino acids and includes alpha-aminoisobutyric acid residues, which are not among the standard proteinogenic set. A C20 fatty diacid moiety is attached through a linker, allowing the compound to bind serum albumin and extend its circulation time. This albumin binding is the main reason the molecule supports once-weekly administration rather than more frequent dosing. The measured molecular mass is approximately 4,813 daltons, placing it firmly in the peptide rather than small-molecule class.
| 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 |
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。
质量控制环节关注外观、含量、纯度、有关物质、水分与微生物限度等项目。检测结果需要有对照品和系统适用性数据支持，单次测定不足以判定批次的稳定性。实验室之间方法转移时，色谱柱品牌与梯度差异常导致保留时间漂移，因此方法验证十分必要。
In clinical research, tirzepatide has been studied in randomized controlled trials for glycemic control and body weight reduction. These trials typically measure changes in hemoglobin A1c and body weight over periods of several months. The drug is administered by subcutaneous injection, and its pharmacokinetic profile supports once-weekly dosing. Post-marketing surveillance continues to evaluate long-term outcomes and rare adverse events.
Tirzepatide is a synthetic peptide that acts as a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The molecule contains 39 amino acids and features a C20 fatty diacid moiety attached via a linker, which promotes albumin binding and extends its circulating half-life. Its sequence incorporates non-natural amino acids and modifications that reduce susceptibility to degradation by dipeptidyl peptidase-4. This dual receptor activity distinguishes it from selective GLP-1 receptor agonists.
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.
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.
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.
The first fully synthetic opioid was meperidine (Demerol), found serendipitously by German chemist Otto Eisleb (or Eislib) at IG Farben in 1932. Meperidine was the first opioid to have a structure unrelated to morphine, but with opioid-like properties. Its analgesic effects were discovered by Otto Schaumann in 1939. Gustav Ehrhart and Max Bockmühl, also at IG Farben, built on the work of Eisleb and Schaumann. They developed "Hoechst 10820" (later methadone) around 1937. In 1959 the Belgian physician Paul Janssen developed fentanyl, a synthetic opioid with 30 to 50 times the potency of heroin. Nearly 150 synthetic opioids are now known.
== Discovery and ownership background == On 1 November 2005, Cambridge Antibody Technology (CAT) announced it was acquiring two anti-CD22 immunotoxin products from Genencor, namely GCR-3888 and GCR-8015. Genencor is the biotechnology division of Danisco and the acquisition meant CAT would hire certain former Genencor key employees to be responsible for the development of the programmes. GCR-3888 and GCR-8015 were discovered and initially developed by the National Cancer Institute, which is part of the U.S. National Institutes of Health. Genencor licensed the candidates for hematological malignancies and entered into a Cooperative Research and Development Agreement (CRADA) with the NIH, which will now be continued by CAT. Under the original license agreement with the NIH, CAT gained the rights to a portfolio of intellectual property associated with the programs and would pay future royalties to the NIH. CAT intended to file an Investigational New Drug (IND) application for GCR-8015 in various CD22 positive B-cell malignancies, including Non-Hodgkin lymphoma and chronic lymphocytic leukemia, following a period of manufacturing development which is expected to be complete by the end of 2006 and to support the NCI's ongoing development of GCR-3888 in Hairy cell leukemia (HCL) and pediatric acute lymphoblastic leukemia (pALL). CAT-8015 exhibited a greater affinity for CD22 than its predecessor, CAT-3888 and CAT's language such as "CAT will support the NCI's ongoing development of CAT-3888..." suggested at the time that their focus was on the second generation candidate.
A number of studies suggest that the inflated rates of depression and anxiety in transgender individuals may partially be because of systematic discrimination or a lack of support. Evidence suggests that these increased rates begin to normalize when transgender individuals are accepted as their identified gender and when they live within a supportive household. Many studies report extremely high rates of suicide within the transgender community. A United States study of 6,450 transgender individuals found that 41% of them had attempted suicide, as differing from the national average of 4.6%. The very same survey found that these rates were the most high for certain demographics, with transgender youth between the ages of 18 and 24 having the highest percent. Individuals in the survey who were multiracial, had lower levels of education, and those with a lower annual income were all more likely to have attempted. Specifically, transgender males as a group are the most likely to attempt suicide, more so than transgender females. Later surveys suggest that the rate of suicidal attempts for non-binary individuals is in between the two. Transgender adults who have "de-transitioned", meaning having gone back to living as their sex assigned at birth, are significantly more likely to attempt suicide than transgender adults who have never "de-transitioned". Several studies have shown the relation between minority stress and the heightened rate of depression and other mental illness among both transgender men and women.
==== Peripheral nervous system ==== Eight to ten nerves arise from the cerebral ganglia to supply the prostomium, buccal chamber and pharynx. Three pairs of nerves arise from the subpharyngeal ganglia to supply the second, third and fourth segment. Three pairs of nerves extend from each segmental ganglion to supply various structures of the segment. The sympathetic nervous system consists of nerve plexuses in the epidermis and alimentary canal. The nerves that run along the body wall pass between the outer circular and inner longitudinal muscle layers of the wall. They give off branches that form the intermuscular plexus and the subepidermal plexus. These nerves connect with the cricopharyngeal connective.
Sources: en.wikipedia.org
Sanjay Kalra (born 18 April 1970) is an Indian endocrinologist working at Bharti Hospital in Karnal, Haryana. Kalra is a former president of the Endocrine Society of India, the South Asian Federation of Endocrine Societies, and the Indian Professional Association for Transgender Health. He has also served on the executive council of the Research Society for the Study of Diabetes in India. Kalra has more than 1,000 PubMed-indexed articles to his credit, and has contributed to strengthening bilateral and multilateral collaborations between various African and Asian countries in the field of endocrinology. He has developed several terms and concepts, including glucokathexis, lipokathexis, glucocrinology, ipocrinology, glycaemic hygiene, endocrine hygiene, and ergonomic endocrinology. He also invented the GlucoCoper tool to assess psychological coping mechanisms in people with diabetes. In addition, he has published work on the concepts of diabetes fatigue syndrome, euthymia in diabetes, quaternary prevention in endocrinology, and quinary prevention.
Scientists and scholars from different countries visited the salon regularly to discuss ideas and share knowledge, and Sablière studied physics, astronomy and natural history with her guests. 1680: French astronomer Jeanne Dumée published a summary of arguments supporting the Copernican theory of heliocentrism. She wrote "between the brain of a woman and that of a man there is no difference". 1685: Frisian poet and archaeologist Titia Brongersma supervised the first excavation of a dolmen in Borger, Netherlands. The excavation produced new evidence that the stone structures were graves constructed by prehistoric humans – rather than structures built by giants, which had been the prior common belief. 1690: German-Polish astronomer Elisabetha Koopman Hevelius, widow of Johannes Hevelius, whom she had assisted with his observations (and, probably, computations) for over twenty years, published in his name Prodromus Astronomiae, the largest and most accurate star catalog to that date. 1693–1698: German astronomer and illustrator Maria Clara Eimmart created more than 350 detailed drawings of the moon phases. 1699: German entomologist Maria Sibylla Merian, the first scientist to document the life cycle of insects for the public, embarked on a scientific expedition to Suriname, South America. She subsequently published Metamorphosis insectorum Surinamensium, a groundbreaking illustrated work on South American plants, animals and insects.
(Studies have also reported that SCFAs inhibit the proliferation and caused apoptosis in cultured human breast cancer MCF-7 and human bladder cancer NaB cells but neither study determined if their actions involved FFAR2.) Further studies are needed to confirm and broaden these preliminary findings and extend them to other types of cancer.
Cipepofol (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name), also known as ciprofol or by its developmental code name HSK3486, sold under the brand name Cypsedo, is a general anesthetic related to propofol which is used for anesthesia and sedation. The drug is used by intravenous infusion. A short-acting and highly selective GABAA positive allosteric modulator, ciprofol is 4 to 6 times more potent than other phenol derivatives such as propofol or fospropofol. In May 2026, cipepofol was approved for medical use in the United States. Manufactured by Haisco Pharmaceutical Group, ciprofol underwent phase I and II trials in Australia and China.
Substantial cephalopelvic disproportion Unfavorable fetal position or presentation (e.g., transverse lies) undeliverable without conversion before delivery Obstetric emergencies where maternal or fetal risk-to-benefit ratio favors surgery Fetal distress when delivery is not imminent Umbilical cord prolapse Uterine activity fails to progress adequately Hyperactive or hypertonic uterus Vaginal delivery is contraindicated (e.g., invasive cervical carcinoma, active genital herpes infection, total placenta previa, vasa previa, cord presentation or prolapse) Uterine or cervical scarring from previous cesarean section or major cervical or uterine (e.g., transfundal) surgery Unengaged fetal head History of hypersensitivity to oxytocin or any ingredient in the formulation
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.
It binds and activates both the GIP and GLP-1 receptors, making it a dual incretin receptor agonist. Single-receptor GLP-1 agonists act on one target only. The dual profile is the defining pharmacological feature of the molecule.