Discovery of hit compounds for methyl-lysine reader proteins from a target class DNA-encoded library

Devan J. Shell,Justin M. Rectenwald,Peter H. Buttery,Rebecca L. Johnson,Caroline A. Foley,Shiva K.R. Guduru,Mélanie Uguen, Juanita Sanchez Rubiano, Xindi Zhang,Fengling Li,Jacqueline L. Norris-Drouin, Matthew Axtman, P. Brian Hardy,Masoud Vedadi,Stephen V. Frye,Lindsey I. James,Kenneth H. Pearce

SLAS Discovery（2022）

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摘要

•Focused DNA-encoded libraries (DELs) are effective in target class hit discovery.•Reader domains of five methyl-lysine reader proteins screened using a focused DEL.•Hit compounds identified from qualitative and quantitative data interpretation.•Compounds validated using primary and secondary biochemical assay characterization.•Identified hit compounds are viable starting points for chemical probe development.

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关键词

DNA-encoded library,Hit discovery,Target class,Chromatin,Reader protein,Methyl-lysine

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