The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer
therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology …

Targeted covalent inhibitors (TCIs) are designed to bind poorly conserved amino acids by
means of reactive groups, the so-called warheads. Currently, targeting noncatalytic cysteine …

Recent advances in chemical proteomics have begun to characterize the reactivity and
ligandability of lysines on a global scale. Yet, only a limited diversity of aminophilic …

Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit
proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been …

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 …

Small molecule degraders such as PROTACs (PROteolysis TArgeting Chimeras) have
emerged as new promising pharmacological modalities and the first PROTAC drug …

Covalent probes can display unmatched potency, selectivity, and duration of action;
however, their discovery is challenging. In principle, fragments that can irreversibly bind their …

Protein kinases are key components in cellular signaling pathways as they carry out the
phosphorylation of proteins, primarily on Ser, Thr, and Tyr residues. The catalytic activity of …

The expansion of the target landscape of covalent inhibitors requires the engagement of
nucleophiles beyond cysteine. Although the conserved catalytic lysine in protein kinases is …

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 …