Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In
mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints …

Targeted covalent inhibitors have regained widespread attention in drug discovery and have
emerged as powerful tools for basic biomedical research. Fueled by considerable …

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

In the first decade of targeted covalent inhibition, scientists have successfully reversed the
previous trend that had impeded the use of covalent inhibition in drug development …

Many drugs currently used are covalent inhibitors and irreversibly inhibit their targets. Most
of these were discovered through serendipity. Covalent inhibitions can have many …

Highlights•Overview on available covalent warheads.•Design principles of covalent
fragment libraries.•Surrogate assay methodologies for testing reactivity.•Covalent screening …

Fragment-based drug discovery (FBDD) has grown and matured to a point where it is
valuable to keep track of its extent and details of application. This Perspective summarizes …

Covalent inhibitors and other types of covalent modalities have seen a revival in the past two
decades, with a variety of new targeted covalent drugs having been approved in recent …

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

Fragment based drug discovery has long been used for the identification of new ligands and
interest in targeted covalent inhibitors has continued to grow in recent years, with high …