PT  - JOURNAL ARTICLE
AU  - Feng Zhu
AU  - LianYi Han
AU  - ChanJuan Zheng
AU  - Bin Xie
AU  - Martti T. Tammi
AU  - ShengYong Yang
AU  - YuQuan Wei
AU  - YuZong Chen
TI  - What Are Next Generation Innovative Therapeutic Targets? Clues from Genetic, Structural, Physicochemical, and Systems Profiles of Successful Targets
AID  - 10.1124/jpet.108.149955
DP  - 2009 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 304--315
VI  - 330
IP  - 1
4099  - http://jpet.aspetjournals.org/content/330/1/304.short
4100  - http://jpet.aspetjournals.org/content/330/1/304.full
SO  - J Pharmacol Exp Ther2009 Jul 01; 330
AB  - Low target discovery rate has been linked to inadequate consideration of multiple factors that collectively contribute to druggability. These factors include sequence, structural, physicochemical, and systems profiles. Methods individually exploring each of these profiles for target identification have been developed, but they have not been collectively used. We evaluated the collective capability of these methods in identifying promising targets from 1019 research targets based on the multiple profiles of up to 348 successful targets. The collective method combining at least three profiles identified 50, 25, 10, and 4% of the 30, 84, 41, and 864 phase III, II, I, and nonclinical trial targets as promising, including eight to nine targets of positive phase III results. This method dropped 89% of the 19 discontinued clinical trial targets and 97% of the 65 targets failed in high-throughput screening or knockout studies. Collective consideration of multiple profiles demonstrated promising potential in identifying innovative targets.