ArticlePloS one2013
Inhibition of nutlin-resistant HDM2 mutants by stapled peptides.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.RSC medicinal chemistry · 2023Review
- The Stapled Peptide PM2 Stabilizes p53 Levels and Radiosensitizes Wild-Type p53 Cancer Cells.Frontiers in oncology · 2019Article
- Synthetic 10FN3-based mono- and bivalent inhibitors of MDM2/X function.Protein engineering, design & selection : PEDS · 2018Article
- Characterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations.Scientific reports · 2017Article
- Article
- Avoiding drug resistance through extended drug target interfaces: a case for stapled peptides.Oncotarget · 2016Article
- The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.Genes & development · 2016Article
- An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide 'stapling' technology.Oncogene · 2015Review
- Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes.Angewandte Chemie (International ed. in English) · 2015Review
- A unique role for p53 in the regulation of M2 macrophage polarization.Cell death and differentiation · 2015Article
- Article
- Drugging the p53 pathway: understanding the route to clinical efficacy.Nature reviews. Drug discovery · 2014Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological modulation of p53 activity is an attractive therapeutic strategy in cancers with wild-type p53. Presently in clinical trials, the small molecule Nutlin-3A competitively binds to HDM2, a key negative regulator of p53 and blocks its activity. We have described resistance mutations in HDM2 that selectively reduce affinity for Nutlin but not p53. In the present communication, we show that stapled peptides targeting the same region of HDM2 as Nutlin are refractory to these mutations, and display reduced discrimination between the wild-type and mutant HDM2s with regards to functional abrogation of interaction with p53. The larger interaction footprint afforded by stapled peptides suggests that this class of ligands may prove comparatively more resilient to acquired resistance in a clinical setting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.