In the first decade of targeted covalent inhibition, scientists have successfully reversed the
previous trend that had impeded the use of covalent inhibition in drug development …

Proteolysis-targeting chimeras (PROTACs) that degrade disease-causing proteins by
hijacking the endogenous ubiquitin-proteasome system have emerged as an exciting and …

Current methods used for measuring amino acid side-chain reactivity lack the throughput
needed to screen large chemical libraries for interactions across the proteome. Here we …

Cysteine chemoproteomics provides proteome-wide portraits of the ligandability or potential"
druggability" for thousands of cysteine residues. Consequently, these studies are facilitating …

Targeted protein degradation (TPD) has emerged as a powerful tool in drug discovery for
the perturbation of protein levels using heterobifunctional small molecules. E3 ligase …

Electrophilic small molecules that can reversibly modify proteins are of growing interest in
drug discovery. However, the ability to study reversible covalent probes in live cells can be …

Here, we report a comprehensive profiling of sulfur (VI) fluorides (SVI-Fs) as reactive groups
for chemical biology applications. SVI-Fs are reactive functionalities that modify lysine …

Heteroaromatic sulfones react with cysteine via nucleophilic aromatic substitution, providing
a mechanistically selective and irreversible scaffold for cysteine conjugation. Here we …

Targeted covalent inhibitors are powerful entities in drug discovery, but their application has
so far mainly been limited to addressing cysteine residues. The development of cysteine …

Targeted protein degradation offers several advantages over direct inhibition of protein
activity and is gaining increasing interest in chemical biology and drug discovery …