Cited by 96Chemical Synthesis and AnalysisComputational Drug Discovery MethodsSynthesis and biological activity

A credit-card library approach for disrupting protein–protein interactions

Xu, Yang, Shi, Jin, Yamamoto, Noboru, Moss, Jason A., Vogt, Peter K., Janda, Kim D.·2006·Bioorganic & Medicinal Chemistry

Abstract

Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in human cancers. Myc belongs to the family of basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factors. It is biologically active only as heterodimer with the bHLH-ZIP protein Max. Herein, we report a new strategy for the disruption of protein-protein interactions that has been corroborated through the design and synthesis of a small parallel library composed of 'credit-card' compounds. These compounds are derived from a planar, aromatic scaffold and functionalized with four points of diversity. From a 285 membered library, several hits were obtained that disrupted the c-Myc-Max interaction and cellular functions of c-Myc. The IC50 values determined for this small focused library for the disruption of Myc-Max dimerization are quite potent, especially since small molecule antagonists of protein-protein interactions are notoriously difficult to find. Furthermore, several of the compounds were active at the cellular level as shown by their biological effects on Myc action in chicken embryo fibroblast assays. In light of our findings, this approach is considered a valuable addition to the armamentarium of new molecules being developed to interact with protein-protein interfaces. Finally, this strategy for disrupting protein-protein interactions should prove applicable to other families of proteins.

Integrity signals

Registry

Crossref · 10.1016/j.bmc.2005.11.052

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

1 of the 68 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Xu, Y., Shi, J., Yamamoto, N., Moss, J. A., Vogt, P. K., & Janda, K. D.
Affiliations
Scripps Research Institute (US)
Corresponding author
  • Vogt, Peter K.
  • Janda, Kim D.
Venue
Bioorganic & Medicinal Chemistry
Publisher
Elsevier BV
Published
2006-04
Volume
14
Issue
8
Pages
2660-2673
ISSN
0968-0896 (ISSN-L)
OpenAlex
W2087562553
Cited by
93
References
68
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 3 · 2012: 8
FWCI
2.26
Type
journal article
Language
en
Open access
closed
Locations
  • Bioorganic & Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
protein-protein interaction disruption, c-Myc, Max, bHLH-Zip transcription factors, small organic molecules, focused compound libraries, cancer therapeutics, chicken embryo fibroblasts
MeSH terms
Animals, Cells, Cultured, Chickens, Circular Dichroism, Humans, Magnetic Resonance Spectroscopy, Protein Binding, DNA Probes, Proto-Oncogene Proteins c-myc, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Electrophoretic Mobility Shift Assay, Fluorescence Resonance Energy Transfer, Basic-Leucine Zipper Transcription Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review