设计同时具有血脑屏障渗透性和脑内分配性的最佳药物。

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-25 DOI:10.1080/17460441.2023.2294118
Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata
{"title":"设计同时具有血脑屏障渗透性和脑内分配性的最佳药物。","authors":"Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata","doi":"10.1080/17460441.2023.2294118","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.</p><p><strong>Areas covered: </strong>This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.</p><p><strong>Expert opinion: </strong>Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition.\",\"authors\":\"Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata\",\"doi\":\"10.1080/17460441.2023.2294118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.</p><p><strong>Areas covered: </strong>This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.</p><p><strong>Expert opinion: </strong>Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.</p>\",\"PeriodicalId\":12267,\"journal\":{\"name\":\"Expert Opinion on Drug Discovery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2024-03-01\",\"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/10.1080/17460441.2023.2294118\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/25 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/10.1080/17460441.2023.2294118","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

导言:随着全球神经系统疾病的发病率和流行率不断上升,人们迫切需要新的药物疗法。BBB能有效保护大脑,但也给药物渗透带来了巨大挑战,大多数药物只有不到2%能进入中枢神经系统:本文回顾了最新设计策略的各个方面,深入探讨了中枢神经系统药物发现的理念和概念。专家观点:在现有的中枢神经系统药物中,小分子药物和中枢神经系统药物的疗效最佳:在现有的中枢神经系统药物中,小分子药物是最成功的中枢神经系统治疗药物,因为它们能够通过被动或载体介导的机制穿透生物BB。开发新的中枢神经系统药物非常困难。迄今为止,还缺乏有效的药物来缓解甚至逆转脑部疾病的进展。尤其是人工智能策略的使用,再加上更合适的动物模型,可以设计出具有适当渗透性的分子,从而引起神经治疗靶点的生物反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition.

Introduction: With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.

Areas covered: This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.

Expert opinion: Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信