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Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC

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Boike, Lydia, Cioffi, Alexander G., Majewski, Felix C., Co, Jennifer, Henning, Nathaniel J., Jones, Michael D., Liu, Gang, McKenna, Jeffrey M., Tallarico, John A., Schirle, Markus, Nomura, Daniel K.·2021·Cell Chemical Biology

DOI 10.1016/j.chembiol.2020.09.001PMC PMC7854864

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Abstract

MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. Here, we have performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt the binding of MYC to its DNA consensus sequence in vitro and also impair MYC transcriptional activity in situ in cells. We have identified a covalent ligand, EN4, that targets cysteine 171 of MYC within a predicted intrinsically disordered region of the protein. We show that EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. We also show initial structure-activity relationships of EN4 and identify compounds that show improved potency. Overall, we identify a unique ligandable site within an intrinsically disordered region of MYC that leads to inhibition of MYC transcriptional activity.

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Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., & Cravatt, B. F. (2010) · Nature · doi:10.1038/nature09472 · Cited by 1,684
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Authors: Boike, L., Cioffi, A. G., Majewski, F. C., Co, J., Henning, N. J., Jones, M. D., Liu, G., McKenna, J. M., Tallarico, J. A., Schirle, M., & Nomura, D. K.
Affiliations: University of California, Berkeley (US)
Innovative Genomics Institute (US)
Corresponding author: Nomura, Daniel K.
ORCID: Boike, Lydia
Cioffi, Alexander G.
Majewski, Felix C.
Co, Jennifer
Henning, Nathaniel J.
Jones, Michael D.
McKenna, Jeffrey M.
Tallarico, John A.
Schirle, Markus
Nomura, Daniel K.
Venue: Cell Chemical Biology
Publisher: Elsevier BV
Published: 2021-01
Volume: 28
Issue: 1
Pages: 4-13.e17
ISSN: 2451-9448 (ISSN-L)
2451-9456
DOI: 10.1016/j.chembiol.2020.09.001
PMC: PMC7854864
OpenAlex: W3089235055
Cited by: 154
References: 35
Citations by year: 2026: 25 · 2025: 39 · 2024: 29 · 2023: 17 · 2022: 20 · 2021: 22
FWCI: 4.81
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
Locations: Cell chemical biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health
Mark Foundation For Cancer Research
Novartis Institutes for BioMedical Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords: c-Myc, intrinsically disordered proteins, covalent ligands, protein thermal stability, structure-activity relationship, MYC inhibitors, carcinogenesis
MeSH terms: Cells, Cultured, Cysteine, Dose-Response Relationship, Drug, Humans, Ligands, Molecular Structure, Proto-Oncogene Proteins c-myc

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Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC

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