ArticleNucleic acids research2013
Small molecule induced reactivation of mutant p53 in cancer cells.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Article
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Covalent drug rescue of multiple p53 mutants by stabilizing vinyl sulfone fragments hints to a specific refolding mechanism for R282W.Protein science : a publication of the Protein Society · 2026Article
- Activity of linalool based silver nanoconjugates against brain tumor through in silico, in vitro and in vivo evaluations.Scientific reports · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- Targeting the p53 cancer mutants Y220C, Y220N, and Y220S with the small-molecule stabilizer rezatapopt.Cell death & disease · 2026Article
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- Cellular activity upregulation of the thermolabile p53 cancer mutant Y220C by small molecule indazole derivatives.Cell death discovery · 2025Article
- High-throughput evaluation of genetic variants with prime editing sensor libraries.Nature biotechnology · 2025Article
- PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with aFuture oncology (London, England) · 2025Article
- Small molecules that targeting p53 Y220C protein: mechanisms, structures, and clinical advances in anti-tumor therapy.Molecular diversity · 2025Review
- Dual therapeutic potential of Scoparia dulcis in combating hyperglycemia and inflammation in diabetes through network pharmacology and in silico analysis.Scientific reports · 2025Article
- Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers.Biomolecules · 2025Review
- Review
- Harnessing the TAF1 Acetyltransferase for Targeted Acetylation of the Tumor Suppressor p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SDrug design, development and therapy · 2025Article
- TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review).International journal of molecular medicine · 2025Review
79 more citing papers are in PubMed but not listed here.
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 2 institutions in 1 country.
Funding
Abstract
The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Here, we have identified a compound, PK7088, which is active in vitro: PK7088 bound to the mutant with a dissociation constant of 140 μM and raised its melting temperature, and we have determined the binding mode of a close structural analogue by X-ray crystallography. We showed that PK7088 is biologically active in cancer cells carrying the Y220C mutant by a battery of tests. PK7088 increased the amount of folded mutant protein with wild-type conformation, as monitored by immunofluorescence, and restored its transcriptional functions. It induced p53-Y220C-dependent growth inhibition, cell-cycle arrest and apoptosis. Most notably, PK7088 increased the expression levels of p21 and the proapoptotic NOXA protein. PK7088 worked synergistically with Nutlin-3 on up-regulating p21 expression, whereas Nutlin-3 on its own had no effect, consistent with its mechanism of action. PK7088 also restored non-transcriptional apoptotic functions of p53 by triggering nuclear export of BAX to the mitochondria. We suggest a set of criteria for assigning activation of p53.
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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.