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PDBsum entry 4w9c
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103 a.a.
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86 a.a.
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141 a.a.
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88 a.a.
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88 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure-Guided design and optimization of small molecules targeting the protein-Protein interaction between the von hippel-Lindau (vhl) e3 ubiquitin ligase and the hypoxia inducible factor (hif) alpha subunit with in vitro nanomolar affinities.
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Authors
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C.Galdeano,
M.S.Gadd,
P.Soares,
S.Scaffidi,
I.Van molle,
I.Birced,
S.Hewitt,
D.M.Dias,
A.Ciulli.
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Ref.
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J Med Chem, 2014,
57,
8657-8663.
[DOI no: ]
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PubMed id
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Abstract
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E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system,
however, the development of small-molecule ligands has been rewarded with
limited success. The von Hippel-Lindau protein (pVHL) is the substrate
recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation.
We recently reported inhibitors of the pVHL:HIF-1α interaction, however they
exhibited moderate potency. Herein, we report the design and optimization,
guided by X-ray crystal structures, of a ligand series with nanomolar binding
affinities.
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