{"title":"环肽药物时代的到来:发现技术的最新进展。","authors":"Sophia You, Glen McIntyre, Toby Passioura","doi":"10.1080/17460441.2024.2367024","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Cyclic peptides are an established class of pharmaceuticals, with the ability to bind to a broader range of protein targets than traditional small molecules while also being capable of oral availability and cell penetration. Historically, cyclic peptide drugs have been discovered almost exclusively through natural product mining approaches; however, the last two decades have seen the development of display screening approaches capable of rapidly identifying <i>de novo</i> (i.e. not natural product derived) cyclic peptide ligands to targets of interest.</p><p><strong>Areas covered: </strong>In this review, the authors describe the current clinical landscape for cyclic peptide pharmaceuticals. This article focuses on the discovery approaches that have led to the development of different classes of molecules and how the development of newer technologies, particularly phage and mRNA display, has broadened the clinical applicability of such molecules.</p><p><strong>Expert opinion: </strong>The field of <i>de novo</i> cyclic peptide drug discovery is reaching maturity, with the first drugs identified through display screening approaches reaching the market in recent years. Many more are in clinical trials; however, significant technical challenges remain. Technological improvements will be required over the coming years to facilitate the identification of membrane permeable cyclic peptides capable of oral availability and targeting intracellular proteins.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The coming of age of cyclic peptide drugs: an update on discovery technologies.\",\"authors\":\"Sophia You, Glen McIntyre, Toby Passioura\",\"doi\":\"10.1080/17460441.2024.2367024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Cyclic peptides are an established class of pharmaceuticals, with the ability to bind to a broader range of protein targets than traditional small molecules while also being capable of oral availability and cell penetration. Historically, cyclic peptide drugs have been discovered almost exclusively through natural product mining approaches; however, the last two decades have seen the development of display screening approaches capable of rapidly identifying <i>de novo</i> (i.e. not natural product derived) cyclic peptide ligands to targets of interest.</p><p><strong>Areas covered: </strong>In this review, the authors describe the current clinical landscape for cyclic peptide pharmaceuticals. This article focuses on the discovery approaches that have led to the development of different classes of molecules and how the development of newer technologies, particularly phage and mRNA display, has broadened the clinical applicability of such molecules.</p><p><strong>Expert opinion: </strong>The field of <i>de novo</i> cyclic peptide drug discovery is reaching maturity, with the first drugs identified through display screening approaches reaching the market in recent years. Many more are in clinical trials; however, significant technical challenges remain. Technological improvements will be required over the coming years to facilitate the identification of membrane permeable cyclic peptides capable of oral availability and targeting intracellular proteins.</p>\",\"PeriodicalId\":12267,\"journal\":{\"name\":\"Expert Opinion on Drug Discovery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17460441.2024.2367024\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17460441.2024.2367024","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
The coming of age of cyclic peptide drugs: an update on discovery technologies.
Introduction: Cyclic peptides are an established class of pharmaceuticals, with the ability to bind to a broader range of protein targets than traditional small molecules while also being capable of oral availability and cell penetration. Historically, cyclic peptide drugs have been discovered almost exclusively through natural product mining approaches; however, the last two decades have seen the development of display screening approaches capable of rapidly identifying de novo (i.e. not natural product derived) cyclic peptide ligands to targets of interest.
Areas covered: In this review, the authors describe the current clinical landscape for cyclic peptide pharmaceuticals. This article focuses on the discovery approaches that have led to the development of different classes of molecules and how the development of newer technologies, particularly phage and mRNA display, has broadened the clinical applicability of such molecules.
Expert opinion: The field of de novo cyclic peptide drug discovery is reaching maturity, with the first drugs identified through display screening approaches reaching the market in recent years. Many more are in clinical trials; however, significant technical challenges remain. Technological improvements will be required over the coming years to facilitate the identification of membrane permeable cyclic peptides capable of oral availability and targeting intracellular proteins.
期刊介绍:
Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
The Editors welcome:
Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology
Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug
The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.