Azaindoles as Zinc-Binding Small-Molecule Inhibitors of the JAMM Protease CSN5 (pages 1294–1297)
Dr. Eva Altmann, Dr. Paul Erbel, Dr. Martin Renatus, Dr. Michael Schaefer, Dr. Anita Schlierf, Adelaide Druet, Laurence Kieffer, Mickael Sorge, Keith Pfister, Dr. Ulrich Hassiepen, Matthew Jones, Dr. Simon Ruedisser, Daniela Ostermeier, Dr. Bruno Martoglio, Dr. Anne B. Jefferson and Dr. Jean Quancard
Version of Record online: 16 DEC 2016 | DOI: 10.1002/anie.201608672
CSN5 is the zinc metalloprotease subunit of the COP9 signalosome, which is an important regulator of cullin-RING E3 ubiquitin ligases. A new class of CSN5 inhibitors (orange) was discovered and shown to interact with the active-site zinc ion in an unprecedented binding mode. Optimized nanomolar CSN5 inhibitors result in decreased levels of the oncoprotein Skp2 and reduce the viability of HCT116 cells.