3MNR

Crystal Structure of Benzamide SNX-1321 bound to Hsp90

Summary for 3MNR

• Entry DOI: 10.2210/pdb3mnr/pdb
• Related: 3D0B
• Descriptor: Heat shock protein HSP 90-alpha, 2-[(3,4,5-trimethoxyphenyl)amino]-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide (3 entities in total)
• Functional Keywords: hsp90, heat shock protein 90, protein-ligand complex, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26634.93

Authors

Veal, J.M.,Fadden, P.,Huang, K.H.,Rice, J.,Hall, S.E.,Haytstead, T.A. (deposition date: 2010-04-22, release date: 2010-08-11, Last modification date: 2023-09-06)

Primary citation

Fadden, P.,Huang, K.H.,Veal, J.M.,Steed, P.M.,Barabasz, A.F.,Foley, B.,Hu, M.,Partridge, J.M.,Rice, J.,Scott, A.,Dubois, L.G.,Freed, T.A.,Silinski, M.A.,Barta, T.E.,Hughes, P.F.,Ommen, A.,Ma, W.,Smith, E.D.,Spangenberg, A.W.,Eaves, J.,Hanson, G.J.,Hinkley, L.,Jenks, M.,Lewis, M.,Otto, J.,Pronk, G.J.,Verleysen, K.,Haystead, T.A.,Hall, S.E.
Application of Chemoproteomics to Drug Discovery: Identification of a Clinical Candidate Targeting Hsp90.
Chem.Biol., 17:686-694, 2010

PubMed Abstract: A chemoproteomics-based drug discovery strategy is presented that utilizes a highly parallel screening platform, encompassing more than 1000 targets, with a focused chemical library prior to target selection. This chemoproteomics-based process enables a data-driven selection of both the biological target and chemical hit after the screen is complete. The methodology has been exemplified for the purine binding proteome (proteins utilizing ATP, NAD, FAD). Screening of an 8000 member library yielded over 1500 unique protein-ligand interactions, which included novel hits for the oncology target Hsp90. The approach, which also provides broad target selectivity information, was used to drive the identification of a potent and orally active Hsp90 inhibitor, SNX-5422, which is currently in phase 1 clinical studies.

PubMed: 20659681
DOI: 10.1016/j.chembiol.2010.04.015

Experimental method

X-RAY DIFFRACTION (1.9 Å)