While some kinases have been the focus of extensive drug discovery campaigns, others remain largely unexplored. These "understudied" kinases have received significantly less attention, leaving their functions poorly annotated in scientific literature. Cyclin-Dependent Kinase-Like 2 (CDKL2) is one such kinase, with no chemical probes previously developed to facilitate its study. This was set to change with a successful collaboration between Alison Axtman at SGC-UNC and the Bullock group at the Centre for Medicines Discovery at the University of Oxford.

Just as your household has a recycling system for waste, cells have sophisticated mechanisms to break down old or damaged proteins to keep everything running smoothly. This system uses chemical tags called ubiquitin to mark proteins for disposal. Researchers from the Structural Genomics Consortium (SGC) have achieved a significant breakthrough with the development of PFI-7, a chemical probe that interferes with a key enzyme’s ability to attach these ubiquitin tags.