A high throughput screening against GPR68, a novel GPCR target, was performed. An unusually high hit rate was observed even after filtering with a counter screen and removing pan-assay interference compounds. Metal contamination of compounds in the BI screening collection was found to activate the target and led to false positive hits, which necessitated trace metal analysis on representative compounds from the HTS hit set. A set of structural patterns in the screening compounds were found to be indicative of metal contamination. Based on the discovery, we made recommendations on revising screening approaches and hit analysis.

Impact of activation of GPR68 by metal cations on high throughput screening

253rd National Meeting (2017)

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