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This work expands the CKI toolbox to include arginine-targeting warheads and provides a modular framework to overcome point mutation-driven resistance, and provides a modular framework to overcome point mutation-driven resistance.
Aurora kinases, especially AURKA, are critical for mitotic regulation, and their dysregulation is linked to tumorigenesis, making AURKA a promising anticancer target. Conventional ATP-competitive AURKA inhibitors suffer from low subtype selectivity and failure to disrupt noncatalytic functions, resulting in limited the...
The dual-target CDK12/PARP1 inhibitor 20b developed herein represents a novel lead molecule for TNBC drug development and exhibited markedly superior antiproliferative effects compared with single-target inhibitors and effectively reduced pSer2-CTD and PAR levels in TNBC cells.
The first small-molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand are reported, thereby expanding the E3 ligase toolbox and offering a promising strategy for targeted cancer therapy.
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