Vulpetti, Anna, Holzer, Philipp, Schmiedeberg, Niko, Imbach-Weese, Patricia, Pissot Soldermann, Carole, Hollingworth, Greg, Radimerski, Thomas, Thoma, Claudio, Stachyra, Therese-Marie, Wojtynek, Matthias, Chau, Suzanne, Schuffenhauer, Ansgar, Fernandez, Cesar, Schroeder, Martin and Renatus, Martin (2023) Discovery of new binders for DCAF1, an emerging ligase target in the Targeted Protein Degradation field. ACS Medicinal Chemistry Letters. ISSN 1948-58751948-5875

Abstract

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 based on 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.

Item Type:	Article
Keywords:	Virtual screening, Structure-based design, Biophysics, DCAF1, E3 ligase, TPD
Date Deposited:	07 Jul 2023 00:45
Last Modified:	07 Jul 2023 00:45
URI:	https://oak.novartis.com/id/eprint/49705