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• W2761872853 abstract "WD40 repeat (WDR) domain-containing proteins are involved in numerous protein complexes that have been linked to disease. Schapira and colleagues describe recent advances in targeting WDR domains with small molecules to potently inhibit protein–protein interactions, and discuss the potential for the diversity and druggability of WDR domains to open up new pathways for therapeutic intervention. Antagonism of protein–protein interactions (PPIs) with small molecules is becoming more feasible as a therapeutic approach. Successful PPI inhibitors tend to target proteins containing deep peptide-binding grooves or pockets rather than the more common large, flat protein interaction surfaces. Here, we review one of the most abundant PPI domains in the human proteome, the WD40 repeat (WDR) domain, which has a central peptide-binding pocket and is a member of the β-propeller domain-containing protein family. Recently, two WDR domain-containing proteins, WDR5 and EED, as well as other β-propeller domains have been successfully targeted by potent, specific, cell-active, drug-like chemical probes. Could WDR domains be a novel target class for drug discovery? Although the research is at an early stage and therefore not clinically validated, cautious optimism is justified, as WDR domain-containing proteins are involved in multiple disease-associated pathways. The druggability and structural diversity of WDR domain binding pockets suggest that understanding how to target this prevalent domain class will open up areas of disease biology that have so far resisted drug discovery efforts." @default.
• W2761872853 created "2017-10-20" @default.
• W2761872853 creator A5012117525 @default.
• W2761872853 creator A5052371425 @default.
• W2761872853 creator A5057700057 @default.
• W2761872853 creator A5076484281 @default.
• W2761872853 date "2017-10-13" @default.
• W2761872853 modified "2023-10-18" @default.
• W2761872853 title "WD40 repeat domain proteins: a novel target class?" @default.
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