Xiaoyun Lu

Discovery of Arginine-Reactive Covalent Kinase Inhibitors Overcoming Clinical Drug Resistance

Abstract Covalent kinase inhibitors (CKIs) serve as potent therapeutics, yet their development largely depends on conserved cysteine residues. Many kinases lack accessible cysteines or develop resistance mutations at these sites, limiting clinical utility. To diversify targetable...

Design, Synthesis, and Antimicrobial Activity of Novel Cyt- bd Inhibitors Targeting Energy Compensation in Mycobacterium tuberculosis

Abstract 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 te...

Biocatalytic Synthesis of dNTPs from Bacterial Biomass

Abstract Deoxyribonucleoside triphosphates (dNTPs) are crucial reagents widely utilized in nucleic acid amplification. However, current synthesis methods are often plagued by environmental pollution for chemical synthesis and the high costs of phosphate donors for enzymatic synth...

Discovery and Synthesis of Selective Casein Kinase 1δ Degraders for Suppressing Oncogenic NRAS-Mutant Melanoma

Abstract 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. How...

Dual‐Site Covalent Targeting Enables BD2‐Selective BET Inhibition With Potent Antitumor Activity in Mice

ABSTRACT Bromodomain and extra‐terminal (BET) proteins are validated therapeutic targets for cancer, but clinical translation of pan‐BET inhibitors is limited by dose‐limiting toxicities from non‐selective inhibition of BD1/BD2 domains. Herein, we report the first‐ever domain‐sel...

Chemo-Enzymatic Synthesisof Purine 3′-O-Amino-DeoxyribonucleosideTriphosphates

Abstract 3′-O-amino-deoxyribonucleoside triphosphates (3′-ONH2-dNTPs) are crucial reversible terminators for template-independent DNA synthesis. Owing to the structural complexity of purine bases, here we propose a chemo-enzymatic process for the synthesis of purine-type 3′-ONH2-...

p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma

Abstract 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 carcin...