ArticleNature communications2020
An alkaloid initiates phosphodiesterase 3A-schlafen 12 dependent apoptosis without affecting the phosphodiesterase activity.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Anagrelide Remodels the PDE3A-SLFN12 Interactome to Associate with Translation Initiation Machinery in Cancer Cell Lines.Molecular & cellular proteomics : MCP · 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
- Turmeric extracellular vesicles-derived "all-in-one" nanoagent enables full-cycle synergistic immunomodulation of lung cancer.Bioactive materials · 2026Article
- Schlafen 12 Modulation and Targeting in Acute Myeloid Leukemia.Cancer research communications · 2025Article
- Review
- 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
- 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
- Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Anagrelide: A Clinically Effective cAMP Phosphodiesterase 3A Inhibitor with Molecular Glue Properties.ACS medicinal chemistry letters · 2023Article
- Velcrin-induced selective cleavage of tRNANature chemical biology · 2023Article
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Structural, molecular, and functional insights into Schlafen proteins.Experimental & molecular medicine · 2022Review
- Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma.Frontiers in oncology · 2022Article
- Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells.Nature communications · 2021Article
- Review
- Biological Activity of Naturally Derived Naphthyridines.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The promotion of apoptosis in tumor cells is a popular strategy for developing anti-cancer drugs. Here, we demonstrate that the plant indole alkaloid natural product nauclefine induces apoptosis of diverse cancer cells via a PDE3A-SLFN12 dependent death pathway. Nauclefine binds PDE3A but does not inhibit the PDE3A's phosphodiesterase activity, thus representing a previously unknown type of PDE3A modulator that can initiate apoptosis without affecting PDE3A's canonical function. We demonstrate that PDE3A's H840, Q975, Q1001, and F1004 residues-as well as I105 in SLFN12-are essential for nauclefine-induced PDE3A-SLFN12 interaction and cell death. Extending these molecular insights, we show in vivo that nauclefine inhibits tumor xenograft growth, doing so in a PDE3A- and SLFN12-dependent manner. Thus, beyond demonstrating potent cytotoxic effects of an alkaloid natural product, our study illustrates a potentially side-effect-reducing strategy for targeting PDE3A for anti-cancer therapeutics without affecting its phosphodiesterase activity.
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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.