TY - JOUR
T1 - Benchmarking the mechanisms of frequent hitters
T2 - limitation of PAINS alerts
AU - Yang, Zi Yi
AU - Yang, Zhi Jiang
AU - He, Jun Hong
AU - Lyu, Aiping
AU - Liu, Shao
AU - Hou, Ting Jun
AU - Cao, Dong Sheng
N1 - Funding Information:
This work was supported by Changsha Science and Technology Bureau project ( kq2001034 ), Key R&D Program of Zhejiang Province ( 2020C03010 ), National Science Foundation of China ( 81773632 ), Zhejiang Provincial Natural Science Foundation of China ( LZ19H300001 ), and HKBU Strategic Development Fund project ( SDF19-0402-P02 ). The study met with the approval of the University’s review board.
Copyright © 2021 Elsevier Ltd. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - In 2010, the pan-assay interference compounds (PAINS) rule was proposed to identify false-positive compounds, especially frequent hitters (FHs), in biological screening campaigns, and has rapidly become an essential component in drug design. However, the specific mechanisms remain unknown, and the result validation and follow-up processing schemes are still unclear. In this review, a large benchmark collection of >600,000 compounds sourced from databases and the literature, including six common false-positive mechanisms, was used to evaluate the detection ability of PAINS. In addition, 400 million purchasable molecules from the ZINC database were also applied to PAINS screening. The results indicate that the PAINS rule is not suitable for the screening of all types of false-positive results and needs more improvement.
AB - In 2010, the pan-assay interference compounds (PAINS) rule was proposed to identify false-positive compounds, especially frequent hitters (FHs), in biological screening campaigns, and has rapidly become an essential component in drug design. However, the specific mechanisms remain unknown, and the result validation and follow-up processing schemes are still unclear. In this review, a large benchmark collection of >600,000 compounds sourced from databases and the literature, including six common false-positive mechanisms, was used to evaluate the detection ability of PAINS. In addition, 400 million purchasable molecules from the ZINC database were also applied to PAINS screening. The results indicate that the PAINS rule is not suitable for the screening of all types of false-positive results and needs more improvement.
UR - http://www.scopus.com/inward/record.url?scp=85101334684&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2021.02.003
DO - 10.1016/j.drudis.2021.02.003
M3 - Journal article
C2 - 33581116
AN - SCOPUS:85101334684
SN - 1359-6446
VL - 26
SP - 1353
EP - 1358
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 6
ER -