ArticleACS chemical biology2014
Identification and characterization of small molecule human papillomavirus E6 inhibitors.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 74 citations in OpenAlex.
- Covalent inhibitors of human papillomavirus type 16 E6 protein restore p53 function and suppress growth of HPV-driven tumors in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrated computational screening of FDA-approved anticancer drugs as novel HPV-16 E6 inhibitors in cervical cancer.Scientific reports · 2026Article
- Article
- Computational analysis of lupenone derivatives as potential inhibitor of human papillomavirus oncoprotein E6 associated cervical cancer.Scientific reports · 2025Article
- Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer.Journal of molecular cell biology · 2025Review
- Human papilloma virus (HPV) mediated cancers: an insightful update.Journal of translational medicine · 2025Review
- Rational Design of Stapled Covalent Peptide Modifiers of Oncoprotein E6 from Human Papillomavirus.ACS chemical biology · 2025Article
- Discovering Active Chemotherapeutic Agents for Sexually Transmitted Diseases to Inhibit Pathogenic HPV-16-E6 Protein.Current drug discovery technologies · 2025Article
- Towards the elimination of infectious HPV: exploiting CRISPR/Cas innovations.Frontiers in cellular and infection microbiology · 2025Review
- Targeting HSP70-E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer.Journal of medical virology · 2024Article
- Silencing E6/E7 Oncoproteins in SiHa Cells Treated with siRNAs and Oroxylum indicum Extracts Induced Apoptosis by Upregulating p53/pRb Pathways.Applied biochemistry and biotechnology · 2024Article
- Structure of the p53 degradation complex from HPV16.Nature communications · 2024Article
- Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.Current medicinal chemistry · 2024Review
- Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6.Chemical science · 2023Article
- Review
- Deciphering the mechanisms of HPV E6 mutations in the destabilization of E6/E6AP/p53 complex.Biophysical journal · 2022Article
- Activation of E6AP/UBE3A-Mediated Protein Ubiquitination and Degradation Pathways by a Cyclic γ-AA Peptide.Journal of medicinal chemistry · 2022Article
- The Reservoir of Persistent Human Papillomavirus Infection; Strategies for Elimination Using Anti-Viral Therapies.Viruses · 2022Review
- The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China.Virology journal · 2022Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cervical cancer is the sixth most common cancer in women worldwide and the leading cause of women's death in developing countries. Nearly all cervical cancers are associated with infection of the human papillomavirus (HPV). This sexually transmitted pathogen disrupts the cell cycle via two oncoproteins: E6 and E7. Cells respond to E7-mediated degradation of pRB by upregulating the p53 tumor suppressor pathway. However, E6 thwarts this response by binding to the cellular E6-Associating Protein (E6AP) and targeting p53 for degradation. These two virus-facilitated processes pave the way for cellular transformation. Prophylactic HPV vaccines are available, but individuals already infected with HPV lack drug-based therapeutic options. To fill this void, we sought to identify small molecule inhibitors of the E6-E6AP interaction. We designed an ELISA-based high throughput assay to rapidly screen compound libraries, and hits were confirmed in several orthogonal biochemical and cell-based assays. Over 88,000 compounds were screened; 30 had in vitro potencies in the mid-nanomolar to mid-micromolar range and were classified as validated hits. Seven of these hits inhibited p53 degradation in cell lines with HPV-integrated genomes. Two compounds of similar scaffold successfully blocked p53 degradation and inhibited cell proliferation in cells stably transfected with E6. Together, these studies suggest that small molecules can successfully block E6-dependent p53 degradation and restore p53 activity. The compounds identified here constitute attractive starting points for further medicinal chemistry efforts and development into beneficial therapeutics.
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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.