4CWN

Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor

Summary for 4CWN

• Entry DOI: 10.2210/pdb4cwn/pdb
• Related: 4CWF 4CWO 4CWP
• Descriptor: HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-(3,5-dimethoxybenzyl)[1,2,4]triazolo[1,5-c]quinazolin-2-amine (3 entities in total)
• Functional Keywords: chaperone
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P07900
• Total number of polymer chains: 1
• Total formula weight: 26146.30

Authors

Casale, E.,Amboldi, N.,Brasca, G.,Caronni, D.,Colombo, N.,Dalvit, C.,Felder, E.R.,Fogliatto, G.,Isacchi, A.,Mantegani, S.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Casuscelli, F. (deposition date: 2014-04-03, release date: 2014-07-09, Last modification date: 2024-05-08)

Primary citation

Casale, E.,Amboldi, N.,Brasca, M.G.,Caronni, D.,Colombo, N.,Dalvit, C.,Felder, E.R.,Fogliatto, G.,Galvani, A.,Isacchi, A.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Casuscelli, F.
Fragment-Based Hit Discovery and Structure-Based Optimization of Aminotriazoloquinazolines as Novel Hsp90 Inhibitors.
Bioorg.Med.Chem., 22:4135-, 2014

PubMed Abstract: In the last decade the heat shock protein 90 (Hsp90) has emerged as a major therapeutic target and many efforts have been dedicated to the discovery of Hsp90 inhibitors as new potent anticancer agents. Here we report the identification of a novel class of Hsp90 inhibitors by means of a biophysical FAXS-NMR based screening of a library of fragments. The use of X-ray structure information combined with modeling studies enabled the fragment evolution of the initial triazoloquinazoline hit to a class of compounds with nanomolar potency and drug-like properties suited for further lead optimization.

PubMed: 24980703
DOI: 10.1016/J.BMC.2014.05.056

Experimental method

X-RAY DIFFRACTION (1.8 Å)