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PDBsum entry 3inx
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References listed in PDB file
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Key reference
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Title
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Inhibition of hsp90 with pochoximes: sar and structure-Based insights.
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Authors
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S.Barluenga,
J.G.Fontaine,
C.Wang,
K.Aouadi,
R.Chen,
K.Beebe,
L.Neckers,
N.Winssinger.
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Ref.
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Chembiochem, 2009,
10,
2753-2759.
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PubMed id
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Abstract
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The pochoximes, based on the radicicol pharmacophore, are potent inhibitors of
heat shock protein 90 (HSP90) that retain their activity in vivo. Herein we
report an extended library that broadly explores the structure-activity
relationship (SAR) of the pochoximes with four points of diversity. Several
modifications were identified that afford improved cellular efficacy, new
opportunities for conjugation, and further diversifications. Cocrystal
structures of pochoximes A and B with HSP90 show that pochoximes bind to a
different conformation of HSP90 than radicicol and provide a rationale for the
enhanced affinity of the pochoximes relative to radicicol and the pochonins.
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