Journal
BRIEFINGS IN BIOINFORMATICS
Volume 21, Issue 2, Pages 649-662Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bby130
Keywords
innovative targets; first-in-class drugs; clinical trial; druggability; clinical trial speed differentiating feature
Funding
- National Natural Science Foundation of China [81872798]
- National Key Research and Development Program of China [2018YFC0910500]
- Innovation Project on Industrial Generic Key Technologies of Chongqing [cstc2015zdcyztzx120003]
- Fundamental Research Funds for the Central Universities [2018QNA7023, 10611CDJXZ238826, 2018CDQYSG0007, CDJZR14468801, CDJKXB14011]
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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.
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