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Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs

2018; Oxford University Press; Volume: 21; Issue: 2 Linguagem: Inglês

10.1093/bib/bby130

1477-4054

Yinghong Li, Xiao Xu Li, Jia Jun Hong, Yunxia Wang, Jianbo Fu, Hong Yang, Chun Yan Yu, Fengcheng Li, Jie Hu, Weiwei Xue, Yu Jiang, Yu Chen, Feng Zhu,

Viral Infectious Diseases and Gene Expression in Insects

Abstract 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.