Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides

Charoenpattarapreeda, Jiraborrirak; Tan, Yaw Sing; Iegre, Jessica; Walsh, Stephen J.; Fowler, Elaine; Eapen, Rohan S.; Wu, Yuteng; Sore, Hannah F.; Verma, Chandra S.; Itzhaki, Laura; Spring, David R.

doi:10.1039/c9cc04022f

Cited by 36Chemical Synthesis and AnalysisCancer-related Molecular PathwaysSynthesis and biological activity

Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides

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Charoenpattarapreeda, Jiraborrirak, Tan, Yaw Sing, Iegre, Jessica, Walsh, Stephen J., Fowler, Elaine, Eapen, Rohan S., Wu, Yuteng, Sore, Hannah F. +3 more·2019·Chemical Communications

DOI 10.1039/c9cc04022f

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Abstract

An electrophile-bearing linker was developed for the generation of a stapled peptide covalent inhibitor of MDM2 via a two-component CuAAC peptide stapling.

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In the specific field of oncology, one covalent PPI inhibitor has been approved by the FDA, while others have entered clinical trials.
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Authors: Charoenpattarapreeda, J., Tan, Y. S., Iegre, J., Walsh, S. J., Fowler, E., Eapen, R. S., Wu, Y., Sore, H. F., Verma, C. S., Itzhaki, L., & Spring, D. R.
Affiliations: University of Cambridge (GB)
Agency for Science, Technology and Research (SG)
Corresponding author: Spring, David R.
ORCID: Charoenpattarapreeda, Jiraborrirak
Tan, Yaw Sing
Iegre, Jessica
Walsh, Stephen J.
Fowler, Elaine
Eapen, Rohan S.
Wu, Yuteng
Sore, Hannah F.
Verma, Chandra S.
Itzhaki, Laura
Spring, David R.
Venue: Chemical Communications
Publisher: Royal Society of Chemistry (RSC)
Published: 2019
Volume: 55
Issue: 55
Pages: 7914-7917
ISSN: 1359-7345 (ISSN-L)
1364-548X
DOI: 10.1039/c9cc04022f
OpenAlex: W2953238007
Cited by: 35
References: 54
Citations by year: 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 1
FWCI: 1.32
Type: journal article
Language: en
Open access: green
www.repository.cam.ac.uk
Licence: rsc.li/journals-terms-of-use (am, 533 d)
Locations: Chemical Communications (publishedVersion)
PubMed (publishedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: Engineering and Physical Sciences Research Council
Bioinformatics Institute (IAF-PP H17/01/a0/010)
Royal Society
Biotechnology and Biological Sciences Research Council
Medical Research Council
Trinity College, University of Cambridge
AstraZeneca
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords: MDM2, p53, protein-protein interaction inhibitors, stapled peptides, covalent inhibitors, electrophilic warheads, p53-MDM2 interaction, targeted drug design
MeSH terms: Binding Sites, Enzyme Inhibitors, Humans, Lysine, Muramidase, Peptides, Cyclic, Saccharomyces cerevisiae, Sulfones, Proto-Oncogene Proteins c-mdm2, Molecular Dynamics Simulation

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Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides

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