Covalent modifiers represent one of the largest categories of pan-assay interference compounds, compounds that appear as hits in screening assays but in fact do not interact specifically with protein targets. Though many drugs act covalently � in some cases on multiple targets � the possibility of covalent binding is often not recognized when hits are identified from a screening campaign. In some cases, the covalent modification was only determined during the course of the investigation. In other cases, despite being flagged in the literature as problematic, these molecules are still reported as selective inhibitors. Knowing precisely what a given molecule is doing is critical for answering biological questions. This presentation will consider several molecules that modify proteins. It will describe how to identify and exclude covalent modifiers as false positives while acknowledging that even promiscuous covalent modifiers can occasionally provide insights into protein structure and function.

Cryptic covalents and other unknown knowns: Useful or not?

248th National Meeting (2014)

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