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 …

Control of protein levels by nucleic-acid-based technologies has proven to be a useful
research tool but lacks the advantages of small molecules with respect to cell permeability …

Selective degradation of proteins by proteolysis targeting chimeras (PROTACs) offers a
promising potential alternative to protein inhibition for therapeutic intervention. Current …

Small molecule covalent kinase inhibitors (CKIs) have entered a new era in drug discovery,
which have the advantage for sustained target inhibition and high selectivity. An increased …

Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine
5′-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible …

Abstract The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is de-regulated in a
variety of cancers due to mutations in receptor tyrosine kinases (RTKs), negative regulators …

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the
RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations …

Designing covalent inhibitors is increasingly important, although it remains challenging.
Here, we present covalentizer, a computational pipeline for identifying irreversible inhibitors …

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 …

The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological
processes including proliferation, cell cycle control, growth, and survival; common across all …