ArticleOncotarget2016
Avoiding drug resistance through extended drug target interfaces: a case for stapled peptides.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 16 citations in OpenAlex.
- Development of Bifunctional, Raman Active Diyne-Girder Stapled α-Helical Peptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Review
- p53-Mediated Radiosensitization ofBiomolecules · 2021Article
- A stapled peptide mimetic of the CtIP tetramerization motif interferes with double-strand break repair and replication fork protection.Science advances · 2021Article
- Restoring p53 Function in Head and Neck Squamous Cell Carcinoma to Improve Treatments.Frontiers in oncology · 2021Review
- Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks.Nanomaterials (Basel, Switzerland) · 2020Article
- Key Players in the Mutant p53 Team: Small Molecules, Gene Editing, Immunotherapy.Frontiers in oncology · 2020Review
- Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides.Scientific reports · 2019Article
- The Stapled Peptide PM2 Stabilizes p53 Levels and Radiosensitizes Wild-Type p53 Cancer Cells.Frontiers in oncology · 2019Article
- Characterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer drugs often fail due to the emergence of clinical resistance. This can manifest through mutations in target proteins that selectively exclude drug binding whilst retaining aberrant function. A priori knowledge of resistance-inducing mutations is therefore important for both drug design and clinical surveillance. Stapled peptides represent a novel class of antagonists capable of inhibiting therapeutically relevant protein-protein interactions. Here, we address the important question of potential resistance to stapled peptide inhibitors. HDM2 is the critical negative regulator of p53, and is often overexpressed in cancers that retain wild-type p53 function. Interrogation of a large collection of randomly mutated HDM2 proteins failed to identify point mutations that could selectively abrogate binding by a stapled peptide inhibitor (PM2). In contrast, the same interrogation methodology has previously uncovered point mutations that selectively inhibit binding by Nutlin, the prototypical small molecule inhibitor of HDM2. Our results demonstrate both the high level of structural p53 mimicry employed by PM2 to engage HDM2, and the potential resilience of stapled peptide antagonists to mutations in target proteins. This inherent feature could reduce clinical resistance should this class of drugs enter the clinic.
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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.