Cargando…

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-...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
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
_version_ 1783547356124282880
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
work_keys_str_mv AT liyinghong clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT lixiaoxu clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT hongjiajun clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT wangyunxia clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT fujianbo clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT yanghong clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT yuchunyan clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT lifengcheng clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT hujie clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT xueweiwei clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT jiangyuyang clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT chenyuzong clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs
AT zhufeng clinicaltrialsprogressionspeeddifferentiatingfeaturesandswiftnessruleoftheinnovativetargetsoffirstinclassdrugs