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 …

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 …

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 …

Loss of the PTEN tumour suppressor is one of the most common oncogenic drivers across
all cancer types. PTEN is the major negative regulator of PI3K signalling. The PI3Kβ isoform …

The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown impressive clinical efficacy in
a range of B-cell malignancies. However, acquired resistance has emerged, and second …

Covalently bound protein kinase inhibitors have been frequently designed to target
noncatalytic cysteines at the ATP binding site. Thus, it is important to know if a given cysteine …

Despite significant efficacy, one of the major limitations of small-molecule Bruton's tyrosine
kinase (BTK) agents is the presence of clinically acquired resistance, which remains a major …

Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series
of quinoline small molecular compounds (a and 2a) and six series of quinoline derivatives …

Despite recent clinical successes for irreversible drugs, potential toxicities mediated by
unpredictable modification of off-target cysteines represents a major hurdle for expansion of …

A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a
malignancy of the developing sympathetic nervous system, is paramount to improving …