Targeted protein degrader design insights; plus Long COVID, obesity and more

Two studies highlighted results that could inform therapeutic development of compounds that induce targeted protein degradation.

The first study, in Nature Communications, identified 76 E3 ligases as candidates for interacting with proteolysis targeting chimeras (PROTACs), a therapeutic modality that works by ubiquitinating targets and sending them to the proteasome for degradation. PROTACs use a linker to connect separate ligands for a target of interest and an E3 ligase. Currently, only a handful of E3 ligases are used for PROTAC design out of over 600 in the human genome, although several companies are working to expand the E3 ligase universe. The study’s Indiana University scientists created a web portal to assist researchers and drug developers in identifying E3 ligases with promising targeted protein degradation activity against a target of interest...