4BQJ

structure of HSP90 with an inhibitor bound

Summary for 4BQJ

• Entry DOI: 10.2210/pdb4bqj/pdb
• Related: 4BQG
• Descriptor: HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-[2,4-dihydroxy-6-(4-nitrophenoxy)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide (3 entities in total)
• Functional Keywords: hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P07900
• Total number of polymer chains: 1
• Total formula weight: 26196.26

Authors

Casale, E.,Brasca, M.G.,Mantegani, S.,Amboldi, N.,Bindi, S.,Caronni, D.,Ceccarelli, W.,Colombo, N.,DePonti, A.,Donati, D.,Ermoli, A.,Fachin, G.,Felder, E.R.,Ferguson, R.D.,Fiorelli, C.,Guanci, M.,Isacchi, A.,Pesenti, E.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Fogliatto, G. (deposition date: 2013-05-30, release date: 2013-10-23, Last modification date: 2024-05-08)

Primary citation

Brasca, M.G.,Mantegani, S.,Amboldi, N.,Bindi, S.,Caronni, D.,Casale, E.,Ceccarelli, W.,Colombo, N.,De Ponti, A.,Donati, D.,Ermoli, A.,Fachin, G.,Felder, E.R.,Ferguson, R.D.,Fiorelli, C.,Guanci, M.,Isacchi, A.,Pesenti, E.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Fogliatto, G.
Discovery of Nms-E973 as Novel, Selective and Potent Inhibitor of Heat Shock Protein 90 (Hsp90).
Bioorg.Med.Chem., 21:7047-, 2013

PubMed Abstract: Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.

PubMed: 24100158
DOI: 10.1016/J.BMC.2013.09.018

Experimental method

X-RAY DIFFRACTION (2 Å)