Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22
8.5
来源：
Nature
关键字：
PROTAC
发布时间：
2025-11-03 23:54
摘要：
G-6599 is a newly designed monovalent degrader targeting SMARCA2/A4, demonstrating exceptional degradation potency and specificity. It operates through the ubiquitin-proteasome pathway, recruiting the E3 ligase FBXO22, which enhances its therapeutic potential in treating AR-dependent prostate cancers. The study emphasizes the innovative approach of rationally designing degraders from existing ligands, showcasing significant advancements in targeted protein degradation strategies.
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关键证据
G-6599 promotes substantial degradation of SMARCA2 and SMARCA4 with DC50 values of 17 pM and 57 pM.
The selective degradation ability of G-6599 highlights the therapeutic potential of target-anchored monovalent degraders.
G-6599 operates through the ubiquitin-proteasome pathway and the E3 ligase FBXO22.
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AI评分总结
G-6599 is a newly designed monovalent degrader targeting SMARCA2/A4, demonstrating exceptional degradation potency and specificity. It operates through the ubiquitin-proteasome pathway, recruiting the E3 ligase FBXO22, which enhances its therapeutic potential in treating AR-dependent prostate cancers. The study emphasizes the innovative approach of rationally designing degraders from existing ligands, showcasing significant advancements in targeted protein degradation strategies.