Covalent drugs have been used to treat diseases for more than a century, but tools that
facilitate the rational design of covalent drugs have emerged more recently. The purposeful …

Bioorthogonal chemistry represents a class of high-yielding chemical reactions that proceed
rapidly and selectively in biological environments without side reactions towards …

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 …

Electrophilic compounds originating from nature or chemical synthesis have profound effects
on immune cells. These compounds are thought to act by cysteine modification to alter the …

With the discovery of PROteolysis TArgeting Chimeras (PROTACs) twenty years ago,
targeted protein degradation (TPD) has changed the landscape of drug development …

Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer
pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its …

Despite advances in genetic and proteomic techniques, a complete portrait of the proteome
and its complement of dynamic interactions and modifications remains a lofty, and as of yet …

Conspectus One of the biggest bottlenecks in modern drug discovery efforts is in tackling the
undruggable proteome. Currently, over 85% of the proteome is still considered undruggable …

Protein modification by chemical reagents has played an essential role in the treatment of
human diseases. However, the reagents currently used are limited to the covalent …

Highlights•Natural tendency for researchers to focus on a small fraction of the human
proteome.•Pharmacological modulators are one of the best ways of interrogating the …