Semaglutide (link:https://www.bloomtechz.com/synthetic-chemical/peptide/semaglutide-powder-cas-910463-68-2.html) is a drug that belongs to the class of insulin-like peptide-1 receptor agonists (GLP-1 RA).
1. Molecular structure:
The molecular structure of Semaglutide is a synthetic polypeptide with 38 amino acid residues. It is obtained by modifying the structure of natural insulin-like peptide-1 (GLP-1). Structurally, Semaglutide has great similarity to the C-terminus of GLP-1, and has multiple amino acid residue modifications.
2. Molecular formula and molecular weight:
Semaglutide has a chemical formula of C187H291N45O59 and a molecular weight of approximately 4113.6 g/mol.
3. Physical properties:
It is slightly soluble in water and soluble in some organic solvents such as methanol and acetonitrile. The solubility of semaglutide changes with pH.
4. Pharmacological properties:
Semaglutide is an insulin-like peptide-1 receptor agonist whose main pharmacological action is to mimic the action of GLP-1 produced in the body. It binds to the GLP-1 receptor to stimulate the secretion of insulin and inhibit the release of glucagon. In addition, semaglutide can also slow down the emptying rate of the gastrointestinal tract and reduce the absorption of food, thereby reducing blood sugar levels. It also suppresses appetite, increases satiety, and aids in weight management.
5. Pharmacokinetic properties:
The pharmacokinetic properties of semaglutide include absorption, distribution, metabolism and excretion. It is rapidly absorbed after subcutaneous injection, and the time to reach maximum plasma concentration is about 5 days. Due to the long-acting nature of semaglutide, it provides a sustained drug effect. It is mainly metabolized by insulinase and other metabolic pathways, and then excreted by the kidneys and feces.
6. Other features:
Semaglutide has high stability and can be stored under normal storage conditions. During use, its stability is not affected by slight temperature changes, so refrigeration is not required.
Semaglutide (trade name: Ozempic) is an insulin-like peptide-1 receptor agonist (GLP-1 RA) indicated for the treatment of type 2 diabetes. The synthetic method of semaglutide can be divided into multiple steps, mainly including solid-phase synthesis, liquid-phase synthesis and purification steps. The following are the main synthetic methods of Semaglutide:
1. Solid phase synthesis:
- The synthesis of semaglutide usually starts with solid phase synthesis.
- First, the first amino acid residue is immobilized on a solid support by solid phase synthesis.
- Then, protect with an Fmoc protecting group before adding the next amino acid residue.
- After each addition of amino acid residues, use a hydrophilic solvent such as carbon disulfide for elution and cleanup.
2. Liquid phase synthesis:
- Release of the polypeptide chains from the solid support into the liquid phase after the solid phase synthesis is complete.
- Use an acid (such as trifluoroacetic acid) or base (such as n-butylamine) to disconnect the polypeptide chain from the solid support.
- Under appropriate conditions, the polypeptide chain is transferred to the liquid phase for subsequent reactions.
3. Linkage of amino acid residues:
- Removal of the corresponding protecting group, exposing the active group of the amino acid residue.
- Link amino acid residues one by one using an activator such as bis-(1-hydrazino)-1,3-diisopropylcarboimide.
4. Thioether bond formation:
- Introduction of cysteine residues in the polypeptide chain.
- Use appropriate reaction conditions and reducing agents (such as triethylamine-trimercaptopropane) to promote the formation of disulfide bonds between cysteine and other amino acids.
5. Protecting group removal:
- After the polypeptide chain has been assembled, the protecting groups on the amino acid residues need to be removed.
- The Fmoc protecting group can be removed using suitable acidic or basic conditions, and other protecting groups can be removed.
6. Purification and structure confirmation:
- Purification and structure confirmation of Semaglutide after completion of synthesis.
- Purification and validation using chromatographic techniques such as high performance liquid chromatography and mass spectrometry techniques such as mass spectrometry.
It should be noted that the steps mentioned above are the main steps in the synthesis of Semaglutide, and the actual synthesis may involve more intermediate steps and adjustments. Due to patent protection, detailed synthetic routes and conditions may not be disclosed. In addition, the commercial manufacture of semaglutide is usually carried out under strict quality control.
Semaglutide is a insulin-like peptide-1 receptor agonist (GLP-1 RA) developed by the Danish pharmaceutical company Novo Nordisk for the treatment of type 2 diabetes. It has benefits such as lowering blood sugar, reducing weight, and improving insulin resistance. The discovery history of Semaglutide can be traced back to the 1990s, which will be introduced in detail below:
In the early 1990s, Novo Nordisk's research team began investigating the possibility of treating diabetes by mimicking insulin-like peptide-1 (GLP-1). GLP-1 is a hormone secreted by the small intestine that promotes insulin secretion, inhibits glucagon release, and slows gastrointestinal emptying. However, because GLP-1 itself is easily degraded in vivo, its short half-life limits its application as a diabetes treatment drug.
In order to overcome the short half-life of GLP-1 and improve stability, researchers at Novo Nordisk used genetic engineering techniques to modify the amino acid sequence of GLP-1 to produce a more stable and long-lasting analogue, insulin-like Peptide-1 receptor agonist (GLP-1 RA). This innovative study was first reported in 1996.
Over the next few years, the research team further refined and optimized these GLP-1 RAs. They tried a variety of methods, including modifying the amino acid sequence, introducing sugar and fatty acid residues, etc., to enhance the activity and stability of the drug.
In 2005, Novo Nordisk researchers first synthesized semaglutide and confirmed it as a potent GLP-1 RA. Semaglutide has a high affinity for the GLP-1 receptor, can mimic the effect of GLP-1, and has a long-acting effect and can be administered by subcutaneous injection.
Subsequently, clinical trials began to evaluate the efficacy and safety of semaglutide in the treatment of patients with type 2 diabetes. The trials covered different patient populations and dose ranges and compared them with other diabetes drugs.
In 2017, Novo Nordisk published the results of an important clinical trial, saying that Semaglutide had achieved remarkable results in the treatment of type 2 diabetes. The trial, called SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes)-6, involved about 3,000 patients and compared semaglutide, as well as other GLP-1 RAs, with a placebo. The results showed that patients treated with semaglutide showed significant benefits in lowering blood sugar levels, reducing body weight and improving insulin resistance.
Based on the results of these clinical trials, Novo Nordisk submitted a new drug application for Semaglutide to the US Food and Drug Administration (FDA) in 2017 and was approved for marketing at the end of 2017. Subsequently, Semaglutide has also been approved by other countries and regions, and is used as a first-line drug for the treatment of type 2 diabetes.
Semaglutide has since shown promise in other areas as well. For example, recent studies have shown that low doses of semaglutide also have favorable effects on weight management and obesity treatment, making semaglutide a potential anti-obesity drug.
In general, the discovery history of semaglutide can be traced back to the early 1990s. Through the modification and optimization of GLP-1, Novo Nordisk successfully synthesized this long-acting and stable GLP-1 RA, and confirmed the Its efficacy and safety as a drug for the treatment of type 2 diabetes. After years of research and clinical trials, Semaglutide has become an important drug for the treatment of diabetes and obesity.