Curcumin is a constituent (up to∼ 5%) of the traditional medicine known as turmeric. Interest
in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led …

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 …

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 …

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 …

We have previously reported on classes of compounds that can interfere with bioassays via
a number of different mechanisms and termed such compounds Pan Assay INterference …

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

Highlights•High potencies and prolonged effects achievable with covalent drugs may result
in less frequent dosing and improved therapeutic margins for patients.•Covalent inhibition …

The clinical and commercial success of covalent drugs has prompted a renewed and more
deliberate pursuit of covalent and irreversible mechanisms within drug discovery. A covalent …

Drugs with prolonged on-target residence times often show superior efficacy, yet general
strategies for optimizing drug-target residence time are lacking. Here we made progress …

Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the
treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or …