Abstract PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-
degradation strategy that has emerged in recent years. It uses bifunctional small molecules …

Dysregulated cell division, which leads to aberrant cell proliferation, is one of the key
hallmarks of cancer. Therefore, therapeutic targets that block cell division would be effective …

Defining the cellular response to pharmacological agents is critical for understanding the
mechanism of action of small molecule perturbagens. Here, we developed a 96-well-plate …

Targeted protein degradation is a new therapeutic modality based on drugs that destabilize
proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are …

Within druggable target space, new small-molecule modalities, particularly covalent
inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists …

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

Molecular glue compounds induce protein–protein interactions that, in the context of a
ubiquitin ligase, lead to protein degradation. Unlike traditional enzyme inhibitors, these …

Cancer arises from genetic alterations that invariably lead to dysregulated transcriptional
programs. These dysregulated programs can cause cancer cells to become highly …

Abstract Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional
elongation, is a promising target for cancer therapy, particularly for cancers driven by …

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 …