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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; 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30689717
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.
Selo DaSilva