Semaglutide Acetate
[CAS# 1997361-85-9]

Identification

• Classification: Biochemical >> Inhibitor >> G protein coupled receptor(GPCR & G Protein)
• Name: Semaglutide Acetate
• Synonyms: acetic acid;18-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-2-methylpropanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-18-oxooctadecanoic acid
• Molecular Formula: C₁₈₉H₂₉₅N₄₅O₆₁
• Molecular Weight: 4173.63
• CAS Registry Number: 1997361-85-9
• SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@H](CC6=CNC=N6)N.CC(=O)O

Discovory and Applicatios

Semaglutide acetate is a synthetic peptide analogue of human glucagon-like peptide-1 (GLP-1) used as a therapeutic agent in the treatment of type 2 diabetes mellitus and obesity. It functions as a GLP-1 receptor agonist, mimicking the action of endogenous GLP-1 to regulate glucose homeostasis by stimulating insulin secretion and inhibiting glucagon release in a glucose-dependent manner. Semaglutide is structurally modified to enhance its stability against enzymatic degradation and prolong its half-life, allowing for once-weekly dosing. The acetate form refers to the acetate salt of semaglutide, which enhances its formulation stability and solubility for pharmaceutical use.

Semaglutide was developed through structural optimization of the native GLP-1 peptide to address limitations such as rapid degradation by dipeptidyl peptidase-4 (DPP-4) and a short biological half-life. Key modifications include substitution at position 8 of the peptide chain with α-aminoisobutyric acid (Aib), which confers resistance to DPP-4 cleavage. Additionally, a fatty acid side chain is attached via a spacer to lysine at position 26, enabling strong binding to albumin and extending its systemic circulation time. These changes result in a prolonged half-life of approximately one week, making semaglutide suitable for weekly subcutaneous injection.

The discovery and development of semaglutide stemmed from efforts to improve the therapeutic profile of earlier GLP-1 receptor agonists such as liraglutide. Researchers at Novo Nordisk engineered semaglutide to retain high potency at the GLP-1 receptor while enhancing pharmacokinetic properties. The compound advanced through preclinical and clinical development based on its efficacy in reducing blood glucose and body weight, as well as its cardiovascular safety profile.

Semaglutide was first approved in 2017 by regulatory authorities for the treatment of type 2 diabetes under the brand name Ozempic. Subsequent trials demonstrated significant weight reduction effects in individuals with obesity, leading to approval under the brand name Wegovy for chronic weight management. These approvals were based on large-scale clinical trials that showed superior glycemic control and substantial weight loss compared to placebo and other antidiabetic agents. In both indications, semaglutide showed a favorable safety and tolerability profile, with gastrointestinal symptoms such as nausea and vomiting being the most common side effects.

The mechanism of action of semaglutide involves activation of GLP-1 receptors expressed on pancreatic β-cells, which enhances insulin secretion in response to elevated blood glucose. It also suppresses glucagon release from α-cells, delays gastric emptying, and promotes satiety through central nervous system pathways, contributing to reduced food intake. These effects together improve glycemic control and support weight loss, making semaglutide a dual-purpose therapy in metabolic disease.

Semaglutide has also been studied for potential benefits beyond glycemic control and weight reduction. Emerging evidence suggests positive effects on cardiovascular outcomes, renal protection, and liver fat content, particularly in patients with non-alcoholic steatohepatitis (NASH). Ongoing clinical studies are evaluating its efficacy in other metabolic and inflammatory disorders.

The acetate salt form of semaglutide ensures stability in injectable formulations and contributes to its consistent pharmacodynamic profile. It is supplied as a sterile, aqueous solution in pre-filled pens for patient self-administration. The recommended dosing regimen begins with a low dose to minimize gastrointestinal side effects and is gradually increased to the maintenance dose.

As a next-generation GLP-1 receptor agonist, semaglutide acetate represents a major advancement in the treatment of metabolic disorders. Its potent, long-acting, and multifunctional profile has led to its widespread adoption in clinical practice and ongoing investigation for expanded therapeutic indications.