H
Henriëtte M. G. Willems
Researcher at Astex
Publications - 4
Citations - 266
Henriëtte M. G. Willems is an academic researcher from Astex. The author has contributed to research in topics: Drug discovery & Protein–protein interaction. The author has an hindex of 3, co-authored 4 publications receiving 183 citations.
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Journal ArticleDOI
Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery
T.G. Davies,William E. Wixted,Joseph E. Coyle,Charlotte Mary Griffiths-Jones,Keisha Hearn,Rachel McMenamin,David Norton,Sharna J. Rich,Caroline Richardson,Gordon Saxty,Henriëtte M. G. Willems,Alison Jo-Anne Woolford,Joshua E. Cottom,Jen-Pyng Kou,John Yonchuk,Heidi G. Feldser,Yolanda Sanchez,Joseph P. Foley,Brian Bolognese,Gregory A. Logan,Patricia L. Podolin,Hongxing Yan,James F. Callahan,Tom D. Heightman,Jeffrey K. Kerns +24 more
TL;DR: This work resulted in a promising lead compound which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chemical probe to explore the therapeutic potential of disrupting theKEAP1-NRF2 interaction.
Journal ArticleDOI
Structure-Activity and Structure-Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein-Protein Interaction.
Tom D. Heightman,James F. Callahan,Elisabetta Chiarparin,Joseph E. Coyle,Charlotte Mary Griffiths-Jones,Ami S. Lakdawala,Rachel McMenamin,Paul N. Mortenson,David Norton,Torren M. Peakman,Sharna J. Rich,Caroline Richardson,William L. Rumsey,Yolanda Sanchez,Gordon Saxty,Henriëtte M. G. Willems,Lawrence Wolfe,Alison Jo-Anne Woolford,Zining Wu,Hongxing Yan,Jeffrey K. Kerns,T.G. Davies +21 more
TL;DR: A detailed account of the medicinal chemistry campaign leading to the KEAP1-NRF2 molecule is presented, which included exploration and optimization of protein-ligand interactions in three energetic "hot spots" identified by fragment screening.
Journal ArticleDOI
Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction.
David Norton,William G. Bonnette,James F. Callahan,Maria Grazia Carr,Charlotte Mary Griffiths-Jones,Tom D. Heightman,Jeffrey K. Kerns,Hong Nie,Sharna J. Rich,Caroline Richardson,William L. Rumsey,Yolanda Sanchez,Marcel L. Verdonk,Henriëtte M. G. Willems,William E. Wixted,Lawrence Wolfe,Alison Jo-Anne Woolford,Zining Wu,T.G. Davies +18 more
TL;DR: In this paper, the authors used fragment-based drug discovery to develop a tool compound that directly disrupts the protein-protein interaction between NRF2 and KEAP1, which provided an alternative chemotype for lead optimization.
Book ChapterDOI
Structural Biology and Anticancer Drug Design
TL;DR: The screening stage of the drug discovery process is a continually evolving field with new technologies being developed to improve the speed, accuracy, and sensitivity of detecting compounds that bind to the target protein (“hits”).