Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α

Dennis L. Buckley; Jeffrey L. Gustafson; Inge Van-Molle; Anke G. Roth; Hyun Seop Tae; Peter C. Gareiss; William L. Jorgensen; Alessio Ciulli; Craig M. Crews

doi:10.1002/anie.201206231

Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α

Dennis L. Buckley
, Jeffrey L. Gustafson
, Inge Van-Molle
, Anke G. Roth
, Hyun Seop Tae
, Peter C. Gareiss
, William L. Jorgensen
, Alessio Ciulli
, Craig M. Crews

Chemistry

Yale University
University of Cambridge

Research output: Contribution to journal › Article › peer-review

279 Scopus citations

Abstract

By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC₅₀ value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction.

Original language	English
Pages (from-to)	11463-11467
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	51
Issue number	46
DOIs	https://doi.org/10.1002/anie.201206231
State	Published - Nov 12 2012

Keywords

drug design
E3 ubiquitin ligases
protein crystallography
protein-protein interactions
structure-based design

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10.1002/anie.201206231

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title = "Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α",

abstract = "By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC50 value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction.",

keywords = "drug design, E3 ubiquitin ligases, protein crystallography, protein-protein interactions, structure-based design",

author = "Buckley, \{Dennis L.\} and Gustafson, \{Jeffrey L.\} and Inge Van-Molle and Roth, \{Anke G.\} and Tae, \{Hyun Seop\} and Gareiss, \{Peter C.\} and Jorgensen, \{William L.\} and Alessio Ciulli and Crews, \{Craig M.\}",

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doi = "10.1002/anie.201206231",

language = "English",

volume = "51",

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journal = "Angewandte Chemie - International Edition",

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T1 - Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α

AU - Buckley, Dennis L.

AU - Gustafson, Jeffrey L.

AU - Van-Molle, Inge

AU - Roth, Anke G.

AU - Tae, Hyun Seop

AU - Gareiss, Peter C.

AU - Jorgensen, William L.

AU - Ciulli, Alessio

AU - Crews, Craig M.

PY - 2012/11/12

Y1 - 2012/11/12

N2 - By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC50 value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction.

AB - By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC50 value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction.

KW - drug design

KW - E3 ubiquitin ligases

KW - protein crystallography

KW - protein-protein interactions

KW - structure-based design

UR - https://www.scopus.com/pages/publications/84868522211

U2 - 10.1002/anie.201206231

DO - 10.1002/anie.201206231

M3 - Article

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AN - SCOPUS:84868522211

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EP - 11467

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 46

ER -

Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α

Abstract

Keywords

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