Non-Covalent Inhibitors of the 20S Proteasome


  • Carlos García-Echeverría
  • Patricia Imbach
  • Johannes Roesel
  • Peter Fuerst
  • Marc Lang
  • Vito Guagnano
  • Maria Noorani
  • Johann Zimmermann
  • Pascal Furet



Antitumor agents, Drug design, Enzyme inhibitors, Peptidomimetic


Peptidomimetics have been commonly used as lead compounds to design inhibitors with high affinity and specificity for a particular enzyme. The discovery that a 2-aminobenzylstatine derivative originally designed to target an aspartyl protease was able to inhibit specifically and non-covalently the chymotrypsin-like activity of the 20S proteasome represented a unique starting point for our medicinal chemistry endeavor for this target. Utilizing a structure-based design approach, we have been able to improve the potency of this new class of proteasome inhibitors without affecting its in vitro selectivity profile.




How to Cite

C. García-Echeverría, P. Imbach, J. Roesel, P. Fuerst, M. Lang, V. Guagnano, M. Noorani, J. Zimmermann, P. Furet, Chimia 2003, 57, 179, DOI: 10.2533/000942903777679415.