8OGB

Crystal structure of human DCAF1 WD40 repeats (Q1250L) in complex with compound 8

Summary for 8OGB

• Entry DOI: 10.2210/pdb8ogb/pdb
• Related: 8OG5 8OG6 8OG7 8OG8 8OG9 8OGA
• Descriptor: DDB1- and CUL4-associated factor 1, 1,2-ETHANEDIOL, ~{N}'-[2-[1-(4-methoxyphenyl)cyclopropyl]-7-(4-methylpiperazin-1-yl)quinazolin-4-yl]ethane-1,2-diamine, ... (5 entities in total)
• Functional Keywords: dcaf1, e3 ligase, compound, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 42415.72

Authors

Schroeder, M.,Vulpetti, A.,Renatus, M. (deposition date: 2023-03-19, release date: 2023-06-14, Last modification date: 2024-06-19)

Primary citation

Vulpetti, A.,Holzer, P.,Schmiedeberg, N.,Imbach-Weese, P.,Pissot-Soldermann, C.,Hollingworth, G.J.,Radimerski, T.,Thoma, C.R.,Stachyra, T.M.,Wojtynek, M.,Maschlej, M.,Chau, S.,Schuffenhauer, A.,Fernandez, C.,Schroder, M.,Renatus, M.
Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.
Acs Med.Chem.Lett., 14:949-954, 2023

PubMed 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 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.

PubMed: 37465299
DOI: 10.1021/acsmedchemlett.3c00104

Experimental method

X-RAY DIFFRACTION (2.27 Å)