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Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.

Anna VulpettiPhilipp HolzerNiko SchmiedebergPatricia Imbach-WeeseCarole Pissot SoldermannGregory J HollingworthThomas RadimerskiClaudio R ThomaTherese-Marie StachyraMatthias WojtynekMagdalena MaschlejSuzanne ChauAnsgar SchuffenhauerCésar FernándezMartin SchröderMartin Renatus
Published in: ACS medicinal chemistry letters (2023)
In this study, we describe the rapid identification of potent binders for the WD40 repeat domain (WDR) of DCAF1. This was achieved by two rounds of iterative focused screening of a small set of compounds selected on the basis of internal WDR domain knowledge followed by hit expansion. Subsequent structure-based design led to nanomolar potency binders with a clear exit vector enabling DCAF1-based bifunctional degrader exploration.
Keyphrases
  • healthcare
  • small molecule
  • cancer therapy
  • protein protein
  • magnetic resonance imaging
  • magnetic resonance
  • binding protein
  • drug delivery
  • single cell
  • quantum dots