ArticleNature communications2016
Identification of pyrazolopyridazinones as PDEδ inhibitors.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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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
83 citing papers in PubMed, 161 citations in OpenAlex.
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- Computational identification and mechanistic characterization of natural product binders targeting the PDE6D prenyl binding tunnel.Scientific reports · 2026Article
- Targeting a Glutamic Acid in PDEδ with Fluoromethyl-Aryl Electrophiles Impairs K-Ras Signaling.Journal of medicinal chemistry · 2026Article
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- Development of a Genetically Encoded and Potent PDE6D Inhibitor.Chembiochem : a European journal of chemical biology · 2025Article
- Targeted Degradation Technologies Utilizing Autophagy.International journal of molecular sciences · 2025Review
- Targeting KRAS: from metabolic regulation to cancer treatment.Molecular cancer · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- An Improved PDE6D Inhibitor Combines with Sildenafil To InhibitJournal of medicinal chemistry · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Review
- Discovery of Novel PDEδ Autophagic Degraders: A Case Study of Autophagy-Tethering Compound (ATTEC).ACS medicinal chemistry letters · 2024Article
- Molecular Complexity of Colorectal Cancer: Pathways, Biomarkers, and Therapeutic Strategies.Cancer management and research · 2024Review
- DFT and molecular simulation validation of the binding activity of PDEδ inhibitors for repression of oncogenic k-Ras.PloS one · 2024Article
- Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.Life science alliance · 2023Article
- Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype.Nature communications · 2023Article
23 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
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The prenyl-binding protein PDEδ is crucial for the plasma membrane localization of prenylated Ras. Recently, we have reported that the small-molecule Deltarasin binds to the prenyl-binding pocket of PDEδ, and impairs Ras enrichment at the plasma membrane, thereby affecting the proliferation of KRas-dependent human pancreatic ductal adenocarcinoma cell lines. Here, using structure-based compound design, we have now identified pyrazolopyridazinones as a novel, unrelated chemotype that binds to the prenyl-binding pocket of PDEδ with high affinity, thereby displacing prenylated Ras proteins in cells. Our results show that the new PDEδ inhibitor, named Deltazinone 1, is highly selective, exhibits less unspecific cytotoxicity than the previously reported Deltarasin and demonstrates a high correlation with the phenotypic effect of PDEδ knockdown in a set of human pancreatic cancer cell lines.
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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.