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Targeted degradation of CK1δ leads to destabilization of NRASQ61R and attenuation of downstream signaling pathways, establishing targeted degradation of CK1δ as a promising therapeutic strategy for NRAS-mutant melanoma.
This study supports co-targeting Cyt-bd and Cyt-bcc as a therapeutic strategy for drug-resistant tuberculosis by finding a structure–activity relationship study starting from the previously identified Cyt-bd inhibitor 12, leading to the discovery of 17aa (YH-685).
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.
It is discovered that p38β/MAPK11 phosphorylation of BiP promotes stemness and chemoresistance in HCC, revealing a targetable p38β–BiP axis in HCC.
The first-ever domain-selective covalent inhibitor of BET BD2 domains by installing an epoxide warhead onto the scaffold of ABBV-744 is reported, establishing for the first time a novel targeted covalent inhibition (TCI) strategy that engages two weakly nucleophilic residues within a single bromodomain.
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