🔸 50 new CRBN neosubstrates🔸 3 bona fide degraders🔸 MS-proteomic platform expanding druggable proteome All of this packed in single paper❗ by colleagues from NEOsphere Biotechnologies GmbH, ICR Centre for Protein Degradation and St. Jude Children’s Research Hospital – ALSAC Additional highlights✅ Screened 100 CRBN-binders across two cancer cell lines✅ Identified 50 novel CRBN neosubstrates❗✅…
Finding potent small-molecule E3 ligase binders is notoriously tough. Here’s how teams from AstraZeneca, Pharmaron, and X‑Chem collaborated to overcome this challenge and discover a drug‑like ligand for the CHIP/STUB1 protein. Key highlights 🔬 Background and Significance– STUB1/CHIP is a U-box E3 ubiquitin ligase that targets misfolded proteins via interactions with Hsc70/Hsp90.– The currently known…
The microcosmos of biological processes is complex and full of surprises. This is also the case for a new preprint from Richert, Nůsková et al. While developing rabeprazole-thalidomide hybrids as targeted protein degraders, the authors observed rapid, reversible ATP depletion in cells. Surprisingly, this effect was attributed to PROTAC molecules with a certain molecular structure. 𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺Mechanistic…