ArticleACS medicinal chemistry letters2026
Discovery and Structural Optimization of BRD4-Selective Monovalent Direct Degraders.
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Targeted protein degradation (TPD) via the ubiquitin-proteasome system (UPS) is a rapidly advancing drug discovery strategy that enables the selective elimination of pathogenic proteins using small molecules. Here, we report the discovery of BRD4-selective monovalent direct degraders acting through DCAF11, identified by ultrahigh-throughput screening and subsequently optimized through a structure-guided medicinal chemistry campaign. Structure-activity relationship (SAR) studies support a direct degrader mechanism and culminated in the identification of the orally bioavailable compound
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