ArticleJournal of medicinal chemistry2015
PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Spatial artifact detection improves the reproducibility of drug screening experiments.iScience · 2025Article
- Transformer Decoder Learns from a Pretrained Protein Language Model to Generate Ligands with High Affinity.Journal of chemical information and modeling · 2025Article
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- Shengyu decoction ameliorates knee osteoarthritis by inhibiting endoplasmic reticulum stress via Piezo1 channels.Frontiers in pharmacology · 2025Article
- Computational Toxicology Methods in Chemical Library Design and High-Throughput Screening Hit Validation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Mining for Potent Inhibitors through Artificial Intelligence and Physics: A Unified Methodology for Ligand Based and Structure Based Drug Design.Journal of chemical information and modeling · 2024Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter.
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Registered trials
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