Cyclic peptide drugs approved in the last two decades (2001–2021)

Zhang, Huiya; Chen, Shiyu

doi:10.1039/d1cb00154j

Cited by 191 publications

(200 citation statements)

References 151 publications

(142 reference statements)

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“…Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity, and low toxicity that make them an attractive modality for the development of therapeutics [118,119] . Over 40 cyclic peptide drugs are currently in clinical use, and around one new cyclic peptide drug enters the market every year on average [120,121] . Many cyclic peptides occur naturally in plants and animals, [122,123] whereas others have been synthetically engineered to be cyclic [124,125] .…”

Section: Discussionmentioning

confidence: 99%

“…[ 118 , 119 ] Over 40 cyclic peptide drugs are currently in clinical use, and around one new cyclic peptide drug enters the market every year on average. [ 120 , 121 ] Many cyclic peptides occur naturally in plants and animals,[ 122 , 123 ] whereas others have been synthetically engineered to be cyclic. [ 124 , 125 ] The vast majority of clinically approved cyclic peptides behave as antimicrobials and antitumor agents.…”

Section: Discussionmentioning

confidence: 99%

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Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

2022

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Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small-molecule active pharmaceutical ingredients, in linear or cyclic oligo-and polypeptidic actives, including pseudopeptides, has led to the development of dedicated synthetic approaches for the formation of amide bonds starting from, if necessary, suitably protected amino acids. While the use of solid supported reagents is common in traditional peptide synthesis, similar approaches targeting amide bond formation in continuous-flow mode took off more significantly, after a first publication in 2006, only a couple of years ago. Most efforts rely upon the transition of traditional approaches in flow mode, or the combination of solid-phase peptide synthesis principles with flow chemistry, and advantages are mainly seen in improving space-time yields. This Review summarizes and compares the various approaches in terms of basic amide formation, peptide synthesis, and pseudopeptide generation, describing the technological approaches and the advantages that were generated by the specific flow approaches. A final discussion highlights potential future needs and perspectives in terms of greener and more sustainable syntheses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

2022

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“…A few examples of cyclic peptides engaging intracellular targets exist that are either approved for clinical use or in clinical trials ( Zhang and Chen, 2022 ). Romidepsin is a cyclic peptide natural product that targets histone deacetylases and its relatively small size (MW: 541 Da) allows it to pass membranes efficiently ( Li et al, 1996 ; Nakajima et al, 1998 ).…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Macrocyclic Peptides

Pal

Hart

2022

Front. Mol. Biosci.

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Being able to effectively target RNA with potent ligands will open up a large number of potential therapeutic options. The knowledge on how to achieve this is ever expanding but an important question that remains open is what chemical matter is suitable to achieve this goal. The high flexibility of an RNA as well as its more limited chemical diversity and featureless binding sites can be difficult to target selectively but can be addressed by well-designed cyclic peptides. In this review we will provide an overview of reported cyclic peptide ligands for therapeutically relevant RNA targets and discuss the methods used to discover them. We will also provide critical insights into the properties required for potent and selective interaction and suggestions on how to assess these parameters. The use of cyclic peptides to target RNA is still in its infancy but the lessons learned from past examples can be adopted for the development of novel potent and selective ligands.

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“…Cyclic peptides, which exist widely in nature (especially marine organisms), have been found with antitumor, anti-bacterial, anti-inflammatory and anti-viral activities [1]. Thus far, more than 100 cyclic peptide drugs have been developed and utilized in the clinic [2]. Cyclic peptides display stronger metabolic stability than linear peptides, allowing them to have longer effects in vivo because of their constrained ring structure, which prevents cleaving by peptidase [3].…”

Section: Introductionmentioning

confidence: 99%

Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents

et al. 2022

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The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly5 (compound 8) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca2+ concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound 8. Western blotting tests showed that compound 8 could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides.

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Cyclic peptide drugs approved in the last two decades (2001–2021)

Abstract: In this mini-review, we summarized the chemical structure, mechanism of action, and metabolism of cyclic peptide drugs approved in the last two decades. We also examined factors important for the development and utilization in clinical situations.

Cited by 191 publications

References 151 publications

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution

RNA-Binding Macrocyclic Peptides

Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents

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