Cited by 702Cancer-related Molecular PathwaysComputational Drug Discovery MethodsSynthesis and biological activity

Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction

Ding, Ke, Lu, Yipin, Nikolovska-Coleska, Zaneta, Wang, Guoping, Qiu, Su, Shangary, Sanjeev, Gao, Wei, Qin, Dongguang +4 more·2006·Journal of Medicinal Chemistry

Abstract

Potent, specific, non-peptide small-molecule inhibitors of the MDM2-p53 interaction were successfully designed. The most potent inhibitor (MI-63) has a K(i) value of 3 nM binding to MDM2 and greater than 10,000-fold selectivity over Bcl-2/Bcl-xL proteins. MI-63 is highly effective in activation of p53 function and in inhibition of cell growth in cancer cells with wild-type p53 status. MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells.

Integrity signals

Registry

Crossref · 10.1021/jm051122a

Cites

20 of 20 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.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Small-molecule PPI antagonists that disrupt the p53-MDM2 interaction have been identified, including nutlin 3a and MI-219.

    “Small-molecule PPI antagonists that disrupt the p53–MDM2 interaction have been identified, including nutlin 3a96 and MI-219 (Ref. 97).”

    From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [97]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Ding, K., Lu, Y., Nikolovska-Coleska, Z., Wang, G., Qiu, S., Shangary, S., Gao, W., Qin, D., Stuckey, J., Krajewski, K., Roller, P. P., & Wang, S.
Affiliations
  • National Institutes of Health (US)
  • Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, and Life Sciences Institute, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, and Laboratory of Medicinal Chemistry, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702
Venue
Journal of Medicinal Chemistry
Published
2006-05-13
Volume
49
Issue
12
Pages
3432-3435
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W2022416218
Cited by
702
References
20
Citations by year
2026: 19 · 2025: 26 · 2024: 23 · 2023: 23 · 2022: 27 · 2021: 40 · 2020: 32 · 2019: 28 · 2018: 37 · 2017: 35 · 2016: 43 · 2015: 53 · 2014: 67 · 2013: 52 · 2012: 52
FWCI
12.35
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P50CA097248, R01CA121279, P50CA069568, P30CA046592)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
p53-MDM2 interaction, small molecule inhibitors, spirooxindoles, p53 activation, structure-based drug design, tumor cell growth inhibition, non-peptidic inhibitors
MeSH terms
Antineoplastic Agents, Cell Membrane Permeability, Drug Screening Assays, Antitumor, Humans, Indoles, Models, Molecular, Protein Binding, Spiro Compounds, Structure-Activity Relationship, Tumor Suppressor Protein p53, Crystallography, X-Ray, Cell Line, Tumor, Proto-Oncogene Proteins c-mdm2

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