Research report on the weight loss drug of semaglutide

1、 Structural information of semaglutide

Semaglutide is based on the natural human GLP-1 molecule and replaces the 8th amino acid (alanine → alpha aminobutyric acid) and 34th amino acid (lysine → arginine), while connecting the C18 fatty acid side chain through a spacer at the 26th lysine position. The structural formula of Smegglutide is C42H79N13O13, consisting of 17 types of 31 amino acids, including histidine, O-aminoisobutyric acid, glutamic acid, glycyrrhetinic acid, threonine, alanine, serine aspartic acid, valic acid, ester xenonic acid, leucic acid, glutamyl wave, alanine, lysine, isoleucine, tryptophan, and arginine.

CAS number: 99291-20-0.

Molecular weight: 4113.58.

Semaglutide has a half-life of approximately 1 week and is suitable for subcutaneous administration once a week.

2、 Original research patent of Semaglutide

The core compound patent CN101133082B "Acylated GLP-1 Compound" of semaglutide does not expire until March 20, 2026. (Although in June 2021, East China Pharmaceutical, a subsidiary of East China Pharmaceutical, launched a patent challenge to the core compound patent of Megglutide, the former research drug company. In September 2022, the China National Intellectual Property Administration ruled that the core patent CN200680006674.6 of Megglutide was invalid. In February 2023, Novo Nordisk filed an appeal to the Beijing Intellectual Property Court for intellectual property litigation. At present, the compound patent is still in dispute, but the patent information registration platform for listed drugs in China shows that the patent is still "effective".

3、 The synthesis process of semaglutide

The product preparation method (CN101910193) was completed using the biological fermentation combined with chemical synthesis method reported in the original research. After synthesizing the GLP-1 (11-37) fragment using this method and using biological fermentation, the N-terminal amino group and hydroxyl groups of Ser, Thr, and Tyr side chains were not protected and directly reacted with the OSu ester of the side chain.

4. The unit price and estimated global usage of raw materials for semaglutide

According to the sales revenue of various formulations of semaglutide announced by Novo Nordisk, and calculated based on the selling price in the Chinese market, the global demand for Smegglutide API in 2023 is 3974.0kg. At present, the domestic raw material price of semaglutide is 3759 yuan/gram (according to statistics from CITIC Securities), which is several times the price of gold! The price of semaglutide per kilogram is 3.8 million yuan, and the price of 1 ton of semaglutide raw material is 3.8 billion yuan.