Benchmarking the mechanisms of frequent hitters: limitation of PAINS alerts. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: Yang, Zi-Yi; Yang, Zhi-Jiang; He, Jun-Hong; Lu, Ai-Ping; Liu, Shao; Hou, Ting-Jun; Cao, Dong-Sheng
• Is Part Of: Drug discovery today. Volume 26:Issue 6(2021)
• Page Start: 1353
• Page End: 1358
• Publication Date: 2021-06
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2021.02.003
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: PAINS rule is one of the most popular false positive compounds screening rule in drug design. However, for PAINS rule, the specific mechanisms remain unknown, and the result validation and follow-up processing schemes are still unclear. A large benchmark containing more than 600, 000 compounds which includes six common false positive mechanisms are used to evaluate the detection ability of PAINS. PAINS rule is not suitable for the screening of all types of false positives screening and needs more improvement. 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.