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Tesamorelin is a synthetic peptide that belongs to the growth hormone-releasing hormone family and contains the same forty-four amino acid sequence as endogenous GHRH, extended at the amino terminus by a trans-3-hexenoyl group. That small fatty acid modification protects the peptide from rapid cleavage by dipeptidyl peptidase-4, the enzyme that shortens the half-life of native GHRH to only a few minutes. Chemically the compound is produced by solid-phase peptide synthesis, purified by chromatography, and supplied as a sterile lyophilized powder for reconstitution.
Regulatory approval in the United States came in 2010, when the Food and Drug Administration cleared the peptide for the reduction of excess abdominal fat in adults with HIV infection and associated lipodystrophy. The decision rested mainly on two randomized phase 3 trials that enrolled roughly eight hundred patients and ran for twenty-six weeks. Participants receiving active drug showed substantially greater declines in visceral adipose tissue than those receiving placebo, while total body weight changed comparatively little. A reformulated presentation was later approved, and the product has remained a niche therapy rather than a general weight-loss agent.
Signaling begins at the GHRH receptor, a class B G protein-coupled receptor displayed on somatotroph cells of the anterior pituitary. Receptor occupancy activates Gs proteins, which raise adenylyl cyclase activity and intracellular cyclic AMP, in turn driving protein kinase A dependent pathways. The downstream output is synthesis and pulsatile secretion of growth hormone into the bloodstream. Hepatic tissue and peripheral sites respond by increasing insulin-like growth factor 1 production. Somatostatin and IGF-1 itself supply negative feedback that caps the size and duration of each secretory burst.
Metabolic interest in this compound centers on fat distribution rather than on hormone levels alone. Imaging trials in adults with excess abdominal fat report reductions in visceral adipose tissue, while subcutaneous depots change comparatively little. Growth hormone and IGF-1 are presumed to carry the effect, but the separate contribution of each is not firmly established. Whether these changes persist after treatment stops, and whether they alter longer-term health outcomes, remain open questions that published work does not answer consistently.
Tesamorelin is a synthetic peptide of forty-four amino acids whose sequence reproduces human growth hormone-releasing hormone. Its distinguishing feature sits at the amino terminus, where a trans-3-hexenoyl group replaces the free amine. That acylation slows cleavage by dipeptidyl peptidase IV, an enzyme that otherwise removes the first two residues and inactivates the natural hormone quickly. The modified peptide therefore persists longer in circulation while keeping the same receptor target. It is handled as a lyophilized solid and dissolved shortly before use.
| Property | Value | Notes |
|---|---|---|
| Peptide class | Synthetic GHRH analogue | 44 residues; N-terminal trans-3-hexenoyl group |
| First approval year | 2010 | United States; HIV-associated abdominal fat accumulation |
| Administration route | Subcutaneous injection | Abdominal site; clinician-administered or self-injected |
| Common synonyms | TH9507; tesamorelin acetate | Development code and acetate salt form |
| Originator | Canadian biotechnology firm | Original developer and regulatory sponsor |
Tesamorelin is a synthetic peptide that belongs to the growth hormone-releasing hormone (GHRH) family. Its sequence corresponds to the fully active 44-amino-acid form of human GHRH, with a single structural modification: the addition of a trans-3-hexenoyl group at the N-terminus. That modification is not found in the naturally occurring hormone and was introduced deliberately during development to improve stability against enzymatic degradation. The compound is therefore best described as a stabilized analogue rather than a naturally occurring peptide.
The native hormone is produced in the hypothalamus and acts on the anterior pituitary. Binding of GHRH to its receptor stimulates synthesis and release of growth hormone into circulation. Because the analogue retains the receptor-binding region of the parent sequence, it engages the same receptor and triggers the same downstream signaling. The result is increased growth hormone secretion from pituitary cells, which in turn influences hepatic production of insulin-like growth factor 1. This axis is the basis for the compound's measured biological effects.
Interest in this peptide developed because native GHRH has a short circulating lifetime. The N-terminal modification slows cleavage by dipeptidyl peptidase IV, an enzyme that removes the first two residues of many peptides and terminates their activity. Slower degradation means a longer window of receptor stimulation per administration. This design logic parallels other modified peptide hormones, where a small chemical change at a vulnerable site yields a more durable molecule without altering the core mechanism of action.
RCOCl + R'OH → RCO2R' + HCl (RCO)2O + R'OH → RCO2R' + RCO2H The reactions are irreversible simplifying work-up. Since acyl chlorides and acid anhydrides also react with water, anhydrous conditions are preferred. The analogous acylations of amines to give amides are less sensitive because amines are stronger nucleophiles and react more rapidly than does water. This method is employed only for laboratory-scale procedures, as it is expensive.
Cardiac muscle forms both the atria and the ventricles of the heart. Although this muscle tissue is very similar between cardiac chambers, some differences exist. The myocardium found in the ventricles is thick to allow forceful contractions, while the myocardium in the atria is much thinner. The individual myocytes that make up the myocardium also differ between cardiac chambers. Ventricular cardiomyocytes are longer and wider, with a denser T-tubule network. Although the fundamental mechanisms of calcium handling are similar between ventricular and atrial cardiomyocytes, the calcium transient is smaller and decays more rapidly in atrial myocytes, with a corresponding increase in calcium buffering capacity. The complement of ion channels differs between chambers, leading to longer action potential durations and effective refractory periods in the ventricles. Certain ion currents such as IK(UR) are highly specific to atrial cardiomyocytes, making them a potential target for treatments for atrial fibrillation.
Disulfur decafluoride is a chemical compound with the formula S2F10. It was discovered in 1934 by Denbigh and Whytlaw-Gray. Each sulfur atom of the S2F10 molecule is octahedral, and surrounded by five fluorine atoms and one sulfur atom. The two sulfur atoms are connected by a single bond. In the S2F10 molecule, the oxidation state of each sulfur atoms is +5, but their valency is 6 (they are hexavalent). It is a colorless liquid with a burnt match smell similar to sulfur dioxide.
== History == The drug was first discovered by scientists including Axel Ullrich and H. Michael Shepard at Genentech, Inc. in South San Francisco, CA. Earlier discovery about the neu oncogene by Robert Weinberg's lab and the monoclonal antibody recognizing the oncogenic receptor by Mark Greene's lab also contributed to the establishment of HER2 targeted therapies. Dr. Dennis Slamon subsequently worked on trastuzumab's development. A book about Dr. Slamon's work was made into a television film called Living Proof, that premiered in 2008. Genentech developed trastuzumab jointly with UCLA, beginning the first clinical trial with 15 women in 1992. By 1996, clinical trials had expanded to over 900 women, but due to pressure from advocates based on early success, Genentech worked with the FDA to begin a lottery system allowing 100 women each quarter access to the medication outside the trials. Herceptin was Fast-tracked by the FDA and gained approval in September 1998. Biocon Ltd and its partner Mylan obtained regulatory approval to sell a biosimilar in 2014, but Roche contested the legality of the approval; that litigation ended in 2016, and Biocon and Mylan each introduced their own branded biosimilars.
Sources: en.wikipedia.org
=== Regulatory agencies === In the US, the Food and Drug Administration (FDA) can audit the files of local site investigators after they have finished participating in a study, to see if they were correctly following study procedures. This audit may be random, or for cause (because the investigator is suspected of fraudulent data). Avoiding an audit is an incentive for investigators to follow study procedures. A 'covered clinical study' refers to a trial submitted to the FDA as part of a marketing application (for example, as part of an NDA or 510(k)), about which the FDA may require disclosure of financial interest of the clinical investigator in the outcome of the study. For example, the applicant must disclose whether an investigator owns equity in the sponsor, or owns proprietary interest in the product under investigation. The FDA defines a covered study as "any study of a drug, biological product or device in humans submitted in a marketing application or reclassification petition that the applicant or FDA relies on to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single investigator makes a significant contribution to the demonstration of safety". Alternatively, many American pharmaceutical companies have moved some clinical trials overseas. Benefits of conducting trials abroad include lower costs (in some countries) and the ability to run larger trials in shorter timeframes, whereas a potential disadvantage exists in lower-quality trial management.
the hydride ion (H−), carried by NAD or NADP+ the phosphate group, carried by adenosine triphosphate the acetyl group, carried by coenzyme A formyl, methenyl or methyl groups, carried by folic acid and the methyl group, carried by S-adenosylmethionine Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 1000 enzymes are known to use the coenzyme NADH. Coenzymes are usually continuously regenerated and their concentrations maintained at a steady level inside the cell. For example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine by methionine adenosyltransferase. This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day.
In a survey of US laypersons in December 2021, most people believed the scientifically supported idea that trained bystanders can reverse overdoses with naloxone. A survey of US naloxone prescription programs in 2010 revealed that 21 out of 48 programs reported challenges in obtaining naloxone in the months leading up to the survey, due mainly to either cost increases that outstripped allocated funding or the suppliers' inability to fill orders. The approximate cost of a 1 ml ampoule of naloxone in the US is estimated to be significantly higher than in most other countries. Take-home naloxone programs for people who use opioids are underway in many North American cities. CDC estimates that the US programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its use prevented 10,000 opioid overdose deaths by 2014. In Australia, some forms of naloxone are available "over the counter" in pharmacies free without a prescription under the Take Home Naloxone programme. It comes in single-use filled syringe form similar to law enforcement kits as well as nasal sprays. In 2024, those with a prescription can purchase five doses for around AU$32 or just over AU$6 per dose. In Alberta, in addition to pharmacy distribution, take-home naloxone kits are available and distributed in most drug treatment or rehabilitation centers. In the European Union, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s.
== External links == Clinical trial number NCT02257567 for "A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma" at ClinicalTrials.gov Clinical trial number NCT03274492 for "A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Diffuse Large B-Cell Lymphoma (POLARIX)" at ClinicalTrials.gov
=== Direct DNA template hypothesis === Soviet-American physicist George Gamow was the first to come up with a coherent scheme for protein synthesis from DNA. Based on the Watson-Crick model, he envisaged that the DNA itself is a direct template for protein synthesis. Assuming that the four bases of DNA could produce 20 different combinations as triplets, he suggested that the different amino acids must correspond to a twenty-letter alphabet of the nucleotide sequence. In such configuration, the DNA directly produces proteins from the free molecules of amino acids. In the 13 February 1954 issue of Nature he explained:It seems to me that such translation procedure can be easily established by considering the 'key-and-lock' relation between various amino-acids, and the rhomb-shaped 'holes' formed by various nucleotides in the deoxyribonucleic acid chain... One can speculate that free amino-acids from the surrounding medium get caught into the 'holes' of deoxyribonucleic acid molecules, and thus unite into the corresponding peptide chains.Watson, then at the California Institute of Technology in Massachusetts, also thought up the issue. Unlike Gamow, he realised the possible importance of RNA as an intermediate stage in protein synthesis. He initially imagined that DNA was first converted by chemical reaction to RNA, but then changed his view to DNA as a template for RNA synthesis. This latter model, which he called "not ugly" was starting to become more convincing.
Sources: en.wikipedia.org
The city of Le Havre has some of the oldest sports clubs in France: the Le Havre Rowing Society (1838), the Regatta Society of Le Havre (1838), and Le Havre Athletic Club (1872), doyen of French football and rugby clubs. The city also hosted the sailing events for the 1900 and 1924 Summer Olympics, respectively. Le Havre is dominated by three professional sports teams: the first is the Le Havre AC football team who were relegated from Ligue 1 after the 2008–2009 season but gained promotion back to Ligue 1 in 2023. Its training centre is well-reputed for having trained a number of international French players, including Vikash Dhorasoo, Julien Faubert, Jean-Alain Boumsong, Lassana Diarra, and Steve Mandanda. The second major sports team is Saint Thomas Basketball who represent the city in LNB Pro A. Thirdly the HAC women's team who play in the first division with many international players in its ranks. The team won their first major national title, the Coupe de France for women's handball in 2006. Le Havre Rugby athletic club plays in Fédérale 3 (equivalent to fifth division). The Hockey Club of Le Havre played at the fourth level nationally (Division 3) for the 2008–2009 season. The team is nicknamed the "Dock's du Havre". The maritime side of the city is found in many sports: for example, the tradition of sailing is old. On 29 July 1840 the first French pleasure boat regatta was held. Today, Le Havre is known as a water sports and Seaside resort. The marina can host deepwater vessels around the clock in any weather.
The two substrates of this enzyme are L-lysine and oxidised nicotinamide adenine dinucleotide (NAD+). Its products are (2S)-2,3,4,5-tetrahydropyridine-2-carboxylic acid (1), ammonia, reduced NADH, and a proton. The enzyme is highly specific for L-lysine as substrate, although S-(2-aminoethyl)-L-cysteine can act as a substrate, but more slowly.
Up to the mid-20th century, the mortality rate was around 60–70%, but this has been greatly reduced with advances in medical care. A review of death cap poisoning throughout Europe from 1971 to 1980 found the overall mortality rate to be 22.4% (51.3% in children under ten and 16.5% in those older than ten). This was revised to around 10–15% in surveys reviewed in 1995.
== Expansions and sequels == Half-Life was followed by an expansion pack, Opposing Force, on November 1, 1999, developed by Gearbox Software. Players control Hazardous Environment Combat Unit (HECU) Corporal Adrian Shephard, who fights a new group of aliens, Race X, and Black Ops units after being split from his team. Gearbox developed a second expansion pack, Blue Shift, in which players control Barney Calhoun, a security guard at Black Mesa, as he attempts to escape the facility. It was developed as a bonus campaign for the Dreamcast port of Half-Life, but was released for Windows on June 12, 2001, after the port was canceled. Gearbox created a cooperative multiplayer expansion pack, Decay, exclusively for the PlayStation 2 port of Half-Life which is played through the perspectives of Gina Cross and Colette Green, two Black Mesa scientists. Half-Life 2 was released in 2004. The player controls Freeman 20 years after the Black Mesa incident in the dystopian City 17, where he joins a rebellion against an alien regime. It was followed by the episodic sequels Half-Life 2: Episode One (2006) and Half-Life 2: Episode Two (2007). After cancelling several other Half-Life projects, Valve released Half-Life: Alyx in 2020.
Sources: en.wikipedia.org
It is a laboratory-made peptide of forty-four amino acids whose sequence matches human growth hormone-releasing hormone, with a modified amino terminus. The modification is a short unsaturated fatty acid chain attached to the first residue. This change slows enzymatic breakdown and lengthens the time the peptide stays active in circulation.
The clinical program was designed around HIV-associated lipodystrophy, a condition in which fat accumulates abnormally around the internal organs. Trials enrolled that specific population, so the evidence base covers it rather than the general population. Regulators approved the drug for the studied indication only, and promotion outside it is not permitted.
Growth hormone therapy supplies the finished hormone directly, while this peptide acts upstream and asks the pituitary to secrete its own. That difference means the response depends on a functioning pituitary and on the body's normal feedback loops. It also means the circulating hormone profile is pulsatile rather than a flat, injected level.
The amino acid sequence matches human growth hormone-releasing hormone, but the amino terminus carries a trans-3-hexenoyl group instead of a free amine. That single structural change chiefly affects enzymatic stability rather than receptor selectivity.