Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.
| Autor: | Vulpetti A; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Holzer P; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Schmiedeberg N; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Imbach-Weese P; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Pissot-Soldermann C; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Hollingworth GJ; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Radimerski T; Oncology Drug Discovery, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Thoma CR; Oncology Drug Discovery, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Stachyra TM; Oncology Drug Discovery, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Wojtynek M; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Maschlej M; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Chau S; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Schuffenhauer A; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Fernández C; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Schröder M; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland., Renatus M; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel 4002, Switzerland. |
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| Jazyk: | angličtina |
| Zdroj: | ACS medicinal chemistry letters [ACS Med Chem Lett] 2023 Jun 02; Vol. 14 (7), pp. 949-954. Date of Electronic Publication: 2023 Jun 02 (Print Publication: 2023). |
| DOI: | 10.1021/acsmedchemlett.3c00104 |
| Abstrakt: | 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. Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.) |
| Databáze: | MEDLINE |
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