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Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs
Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004–17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299286/ https://www.ncbi.nlm.nih.gov/pubmed/30689717 http://dx.doi.org/10.1093/bib/bby130 |
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author | Li, Ying Hong Li, Xiao Xu Hong, Jia Jun Wang, Yun Xia Fu, Jian Bo Yang, Hong Yu, Chun Yan Li, Feng Cheng Hu, Jie Xue, Wei Wei Jiang, Yu Yang Chen, Yu Zong Zhu, Feng |
author_facet | Li, Ying Hong Li, Xiao Xu Hong, Jia Jun Wang, Yun Xia Fu, Jian Bo Yang, Hong Yu, Chun Yan Li, Feng Cheng Hu, Jie Xue, Wei Wei Jiang, Yu Yang Chen, Yu Zong Zhu, Feng |
author_sort | Li, Ying Hong |
collection | PubMed |
description | Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004–17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development. |
format | Online Article Text |
id | pubmed-7299286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72992862020-06-22 Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs Li, Ying Hong Li, Xiao Xu Hong, Jia Jun Wang, Yun Xia Fu, Jian Bo Yang, Hong Yu, Chun Yan Li, Feng Cheng Hu, Jie Xue, Wei Wei Jiang, Yu Yang Chen, Yu Zong Zhu, Feng Brief Bioinform Problem Solving Protocol Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004–17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development. Oxford University Press 2019-01-23 /pmc/articles/PMC7299286/ /pubmed/30689717 http://dx.doi.org/10.1093/bib/bby130 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Problem Solving Protocol Li, Ying Hong Li, Xiao Xu Hong, Jia Jun Wang, Yun Xia Fu, Jian Bo Yang, Hong Yu, Chun Yan Li, Feng Cheng Hu, Jie Xue, Wei Wei Jiang, Yu Yang Chen, Yu Zong Zhu, Feng Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title | Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title_full | Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title_fullStr | Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title_full_unstemmed | Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title_short | Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
title_sort | clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs |
topic | Problem Solving Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299286/ https://www.ncbi.nlm.nih.gov/pubmed/30689717 http://dx.doi.org/10.1093/bib/bby130 |
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