Activating NRAS mutations occur in approximately 20% of melanomas but remain largely undruggable due to the lack of effective targeted therapies. We previously identified casein kinase 1δ (CK1δ) as a critical upstream regulator that stabilizes oncogenic NRAS mutants. However, no selective CK1δ inhibitors have advance...
Chang-Fa Zhang, Ya-Lei Wen, Jian-Qiao Yi et al.· Journal of Medicinal Chemist...· 0 citations
Drug-resistant Mycobacterium tuberculosis (Mtb) poses a growing threat, necessitating new therapeutic strategies. The cytochrome bcc-aa3 oxidase (Cyt-bcc) is an attractive target, yet single-agent inhibition fails owing to compensation by the alternative cytochrome bd terminal oxidase (Cyt-bd). Herein, we describe a...
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.
Zu-Qin Wang, Xuan Wang, Hong Zhang et al.· Journal of Medicinal Chemist...· 0 citations
Tumor-initiating cells (TICs) promote tumor initiation and therapy resistance, yet the kinase regulators that sustain TICs remain incompletely defined. Here, we identify the stress kinase p38β (MAPK11) supports TIC maintenance and drug resistance in hepatocellular carcinoma (HCC). Integrated analysis of chemotherapy-en...
Liang Xu, I. B. Huang, Minghe Zhang et al.· Nature Communications· 0 citations
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