TY - JOUR
T1 - Frequent hitters
T2 - nuisance artifacts in high-throughput screening
AU - Yang, Zi Yi
AU - He, Jun Hong
AU - Lu, Ai Ping
AU - Hou, Ting Jun
AU - Cao, Dong Sheng
N1 - Funding Information:
This work was supported by the National Key Basic Research Program (2015CB910700), National Science Foundation of China (21575128, 81773632), Zhejiang Provincial Natural Science Foundation of China (LZ19H300001), and HKBU Strategic Development Fund project (SDF19-0402-P02). The studies meet with the approval of the University's review board.
Publisher copyright:
© 2020 Elsevier Ltd. All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved.
AB - One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved.
UR - http://www.scopus.com/inward/record.url?scp=85078853071&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2020.01.014
DO - 10.1016/j.drudis.2020.01.014
M3 - Review article
C2 - 31987936
AN - SCOPUS:85078853071
SN - 1359-6446
VL - 25
SP - 657
EP - 667
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 4
ER -