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 …

Over the past decade, covalent kinase inhibitors (CKI) have seen a resurgence in drug
discovery. Covalency affords a unique set of advantages as well as challenges relative to …

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling
protein in tumours,. The KRAS (G12C) mutant has a cysteine residue that has been …

KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent
inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by …

We recently described glutathione peroxidase 4 (GPX4) as a promising target for killing
therapy-resistant cancer cells via ferroptosis. The onset of therapy resistance by multiple …

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

Although Michael acceptors display a potent and broad spectrum of bioactivity, they have
largely been ignored in drug discovery because of their presumed indiscriminate reactivity …

Covalent inhibitors of KRASG12C have shown antitumor activity against
advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and …

In contrast to the traditional mechanism of drug action that relies on the reversible,
noncovalent interaction of a ligand with its biological target, a targeted covalent inhibitor …

Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing
the targeting of undruggable proteins for proteasomal degradation. This approach most …