ArticleNature chemical biology2016
Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Preclinical response of uveal melanomas to the velcrin compound, BAY 2666605.Molecular cancer therapeutics · 2026Article
- Pan-cancer ex vivo target evaluation of phosphodiesterase 3 A (PDE3A).Journal of molecular medicine (Berlin, Germany) · 2026Article
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- MGDB: a curated database for molecular glues.Nucleic acids research · 2026Article
- Pharmacokinetic profile andDrug delivery · 2025Article
- Epigenetic and Post-Translational Regulation of Schlafen Family Expression and Their Differential Methods of Regulating Proteins.International journal of molecular sciences · 2025Review
- Schlafen 12 Modulation and Targeting in Acute Myeloid Leukemia.Cancer research communications · 2025Article
- Structural and functional characterization of human SLFN14.Nucleic acids research · 2025Article
- Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.Leukemia · 2025Article
- Establishment and validation of a prognostic model based on vasculogenic mimicry-related gene clustering in ovarian cancer.Frontiers in oncology · 2025Article
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- First-in-Human Dose-Escalation Study of the First-in-Class PDE3A-SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.ACS medicinal chemistry letters · 2024Article
- Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.International journal of clinical oncology · 2024Article
- A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Overview of Structural and Functional Insights of SLFN12 Associated With Different Diseases.Cureus · 2024Review
- Discovery of Molecular Glue Degraders via Isogenic Morphological Profiling.ACS chemical biology · 2023Article
- Article
- Molecular Glue Discovery: Current and Future Approaches.Journal of medicinal chemistry · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors.
Funding
Abstract
High cancer death rates indicate the need for new anticancer therapeutic agents. Approaches to discovering new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds through phenotypic compound library screening and target deconvolution by predictive chemogenomics. We found that sensitivity to 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, across 766 cancer cell lines correlates with expression of the gene PDE3A, encoding phosphodiesterase 3A. Like DNMDP, a subset of known PDE3A inhibitors kill selected cancer cells, whereas others do not. Furthermore, PDE3A depletion leads to DNMDP resistance. We demonstrated that DNMDP binding to PDE3A promotes an interaction between PDE3A and Schlafen 12 (SLFN12), suggestive of a neomorphic activity. Coexpression of SLFN12 with PDE3A correlates with DNMDP sensitivity, whereas depletion of SLFN12 results in decreased DNMDP sensitivity. Our results implicate PDE3A modulators as candidate cancer therapeutic agents and demonstrate the power of predictive chemogenomics in small-molecule discovery.
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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.