ArticleOncogene2017
Mechanistic validation of a clinical lead stapled peptide that reactivates p53 by dual HDM2 and HDMX targeting.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 41 citations in OpenAlex.
- Delivery of ATSP-7041 by Minimally Invasive Nasal Depot (MIND) to Target Diffuse Intrinsic Pontine Glioma.Molecular cancer therapeutics · 2026Article
- Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.Journal of medicinal chemistry · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.Nature communications · 2024Article
- Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro.Biomolecules · 2023Article
- Article
- Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins.Advanced healthcare materials · 2022Review
- Utilization of macrocyclic peptides to target protein-protein interactions in cancer.Frontiers in oncology · 2022Review
- Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions.PloS one · 2022Article
- Article
- Article
- Current developments of targeting the p53 signaling pathway for cancer treatment.Pharmacology & therapeutics · 2021Review
- Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles.Chemical science · 2019Article
- Identification of selective protein-protein interaction inhibitors using efficientChemical science · 2019Article
- In-solution enrichment identifies peptide inhibitors of protein-protein interactions.Nature chemical biology · 2019Article
- Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology.Trends in biochemical sciences · 2019Review
- The Potential of Targeting P53 and HSP90 Overcoming Acquired MAPKi-Resistant Melanoma.Current treatment options in oncology · 2019Review
- Augmented antitumor activity of 5-fluorouracil by double knockdown of MDM4 and MDM2 in colon and gastric cancer cells.Cancer science · 2019Article
- Advanced forms of MPNs are accompanied by chromosomal abnormalities that lead to dysregulation of TP53.Blood advances · 2018Article
- Genome-scale CRISPR-Cas9 screen identifies druggable dependencies inThe Journal of experimental medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hydrocarbon-stapled peptides that display key residues of the p53 transactivation domain have emerged as bona fide clinical candidates for reactivating the tumor suppression function of p53 in cancer by dual targeting of the negative regulators HDM2 and HDMX. A recent study questioned the mechanistic specificity of such stapled peptides based on interrogating their capacity to disrupt p53/HDM2 and p53/HDMX complexes in living cells using a new recombinase enhanced bimolecular luciferase complementation platform (ReBiL). Here, we directly evaluate the cellular uptake, intracellular targeting selectivity and p53-dependent cytotoxicity of the clinical prototype ATSP-7041. We find that under standard serum-containing tissue culture conditions, ATSP-7041 achieves intracellular access without membrane disruption, dose-dependently dissociates both p53/HDM2 and p53/HDMX complexes but not an unrelated protein complex in long-term ReBiL experiments, and is selectively cytotoxic to cancer cells bearing wild-type p53 by inducing a surge in p53 protein level. These studies underscore the importance of a thorough stepwise approach, including consideration of the time-dependence of cellular uptake and intracellular distribution, in evaluating and advancing stapled peptides for clinical translation.
Indexed as
Identifiers
What OpenQuestion holds
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.