Cagrilintide
[CAS# 1415456-99-3]

Identification

• Classification: API >> Drugs that affect tissue metabolism
• Name: Cagrilintide
• Synonyms: 20-[[(1S)-4-[[(2S)-6-amino-1-[[(4R,7S,10S,13S,16S,19R)-4-[[(2S)-1-[[(2S,3R)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2R)-4-amino-1-[[(2S)-1-[[2-[(2S)-2-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-16-(2-amino-2-oxoethyl)-7,13-bis[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxohexan-2-yl]amino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid
• Molecular Formula: C₁₉₄H₃₁₂N₅₄O₅₉S₂
• Molecular Weight: 4409.01
• Protein Sequence: XKCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP
• CAS Registry Number: 1415456-99-3
• SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N3CCC[C@H]3C(=O)N)NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@@H]8CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N8)[C@@H](C)O)C)[C@@H](C)O)CC(=O)N)NC(=O)[C@H](CCCCN)NC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O

Discovery and Applications

Kaglinide is a synthetic peptide designed to help with weight management and metabolic health. It stems from research into appetite-regulating hormones and was discovered by scientists at Novo Nordisk in the 2010s. The peptide is a long-acting analog of amylin, a hormone that is co-secreted with insulin from the pancreas and plays a key role in satiety and blood sugar regulation.

Kaglinide works by mimicking the function of amylin. It binds to amylin receptors in the brain, reduces appetite and slows gastric emptying. This results in increased satiety, reduced caloric intake and better blood sugar control. By modulating these processes, Kaglinide helps control weight and improve metabolic parameters.

Kaglinide is primarily used for weight management in patients with obesity or overweight comorbidities. Clinical trials have demonstrated that it is effective in achieving significant weight loss when used alone or in combination with other weight loss medications, such as GLP-1 receptor agonists. Patients treated with Kaglinide experience a decrease in appetite, which helps sustain weight loss and improves blood sugar control.

Kaglinide's ability to enhance satiety makes it a valuable adjunct in combination therapies for weight loss. When used with GLP-1 receptor agonists, it provides complementary benefits by acting on different pathways that regulate appetite and metabolism. This combined approach can lead to stronger weight loss and better control of conditions such as type 2 diabetes.

In addition to its primary application in weight loss, capraglinide is also being studied for its potential benefits in managing metabolic syndrome and related conditions. Its effects in improving glycemic control and reducing appetite make it a candidate for treating conditions such as prediabetes, nonalcoholic fatty liver disease (NAFLD), and obesity-related cardiovascular risk factors.

References

2021. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry, 64(14).
DOI: 10.1021/acs.jmedchem.1c00565

2021. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet, 398(10317).
DOI: 10.1016/s0140-6736(21)01751-7

2023. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet, 402(10403).
DOI: 10.1016/s0140-6736(23)01163-7