Benchmarking the mechanisms of frequent hitters: limitation of PAINS alerts

Zi Yi Yang, Zhi Jiang Yang, Jun Hong He, Aiping LYU, Shao Liu, Ting Jun Hou*, Dong Sheng Cao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1353-1358
Number of pages6
JournalDrug Discovery Today
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 2021

Scopus Subject Areas

  • Pharmacology
  • Drug Discovery

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