Discovery of an Exquisitely Selective WDR5 Chemical Probe Accelerated by a High-Quality DEL-ML Hit

A chemoproteomics experiment was performed to investigate the selectivity of the WDR5 targeting compound LH168. Therefore, a biotinylated adduct of LH168, namely LH205, was used to enrich potential target proteins of LH168. The addition of LH168 in excess competed only the interaction with LH168, demonstrating a proteome wide selectivity of LH168 for WDR5.