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

The ATP site of kinases displays remarkable conformational flexibility when accommodating
chemically diverse small molecule inhibitors. The so-called activation segment, whose …

Background: The investigation of the cellular components, their interactions and related
functions constitute the major conditions in order to understand the cell as an integrated …

Protein kinases regulate the majority of signal transduction pathways in cells and have
become important targets for the development of designer drugs. We present a systematic …

Systems approaches have long been used in pharmacology to understand drug action at
the organ and organismal levels. The application of computational and experimental …

The divalent cation calcium (Ca2+) is considered one of the main second messengers
inside cells and acts as the most prominent signal in a plethora of biological processes. Its …

Fragment-based drug discovery (FBDD) has become established in both industry and
academia as an alternative approach to high-throughput screening for the generation of …

Fragment-based drug discovery typically requires an interplay between screening methods,
structural methods, and medicinal chemistry. X-ray crystallography is generally the method …

Dysregulation of protein–protein interactions (PPIs) commonly leads to disease. PPI
stabilization has only recently been systematically explored for drug discovery despite being …

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