3QTF

Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity

Summary for 3QTF

• Entry DOI: 10.2210/pdb3qtf/pdb
• Descriptor: Heat shock protein HSP 90-alpha, (6S)-6,15,15,18-tetramethyl-17-oxo-2,3,4,5,6,7,14,15,16,17-decahydro-1H-8,12-(metheno)[1,4,9]triazacyclotetradecino[9,8-a]indole-9-carboxamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• Functional Keywords: chaperone, atp binding domain, atp-binding, nucleotide-binding, phosphoprotein, stress response, chaperone-chaperone inhibitor complex, chaperone/chaperone inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 25899.24

Authors

Zapf, C.W.,Bloom, J.D.,McBean, J.L.,Dushin, R.G.,Nittoli, T.,Ingalls, C.,Sutherland, A.G.,Sonye, J.P.,Eid, C.N.,Golas, J.,Liu, H.,Boschelli, F.,Hu, Y.,Vogan, E.M.,Levin, J.I. (deposition date: 2011-02-22, release date: 2011-04-06, Last modification date: 2024-02-21)

Primary citation

Zapf, C.W.,Bloom, J.D.,McBean, J.L.,Dushin, R.G.,Nittoli, T.,Ingalls, C.,Sutherland, A.G.,Sonye, J.P.,Eid, C.N.,Golas, J.,Liu, H.,Boschelli, F.,Hu, Y.,Vogan, E.,Levin, J.I.
Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity.
Bioorg.Med.Chem.Lett., 21:2278-2282, 2011

PubMed Abstract: A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay.

PubMed: 21420297
DOI: 10.1016/j.bmcl.2011.02.101

Experimental method

X-RAY DIFFRACTION (1.5703 Å)