ArticleOncotarget2015
NZ51, a ring-expanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 55 citations in OpenAlex.
- Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025Review
- DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2.FEBS open bio · 2025Article
- DEAD-box helicase family proteins: emerging targets in digestive system cancers and advances in targeted drug development.Journal of translational medicine · 2024Review
- DEAD-box RNA helicases with special reference to p68: Unwinding their biology, versatility, and therapeutic opportunity in cancer.Genes & diseases · 2023Review
- Molecular docking, synthesis, and biological evaluation of 7-azaindole-derivative (7AID) as novel anti-cancer agent and potent DDX3 inhibitor:-an in silico and in vitro approach.Medical oncology (Northwood, London, England) · 2022Article
- Yin Yang 1 promotes aggressive cell growth in high-grade breast cancer by directly transactivating kinectin 1.MedComm · 2022Article
- DEAD-ly Affairs: The Roles of DEAD-Box Proteins on HIV-1 Viral RNA Metabolism.Frontiers in cell and developmental biology · 2022Review
- A Dual Role of DDX3X in dsRNA-Derived Innate Immune Signaling.Frontiers in molecular biosciences · 2022Review
- Targeting DDX3X Helicase Activity with BA103 Shows Promising Therapeutic Effects in Preclinical Glioblastoma Models.Cancers · 2021Article
- The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models.Cancers · 2021Article
- Targeting DDX3X Triggers Antitumor Immunity via a dsRNA-Mediated Tumor-Intrinsic Type I Interferon Response.Cancer research · 2021Article
- Review
- The DEAD-box protein family of RNA helicases: sentinels for a myriad of cellular functions with emerging roles in tumorigenesis.International journal of clinical oncology · 2021Review
- Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines.Frontiers in oncology · 2021Article
- RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2020Review
- Sequence-Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin-3 and Delay Wound Healing of a Galectin-3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay.Macromolecular bioscience · 2020Article
- A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines.Biomolecules · 2020Article
- DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs.Molecules (Basel, Switzerland) · 2020Review
- DDX3X Multifunctionally Modulates Tumor Progression and Serves as a Prognostic Indicator to Predict Cancer Outcomes.International journal of molecular sciences · 2019Review
- Synthesis and Antiviral Activity of Novel 1,3,4-Thiadiazole Inhibitors of DDX3X.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DDX3X (DDX3), a human RNA helicase, is over expressed in multiple breast cancer cell lines and its expression levels are directly correlated to cellular aggressiveness. NZ51, a ring-expanded nucleoside analogue (REN) has been reported to inhibit the ATP dependent helicase activity of DDX3. Molecular modeling of NZ51 binding to DDX3 indicated that the 5:7-fused imidazodiazepine ring of NZ51 was incorporated into the ATP binding pocket of DDX3. In this study, we investigated the anticancer properties of NZ51 in MCF-7 and MDA-MB-231 breast cancer cell lines. NZ51 treatment decreased cellular motility and cell viability of MCF-7 and MDA-MB-231 cells with IC50 values in the low micromolar range. Biological knockdown of DDX3 in MCF-7 and MDA-MB-231 cells resulted in decreased proliferation rates and reduced clonogenicity. In addition, NZ51 was effective in killing breast cancer cells under hypoxic conditions with the same potency as observed during normoxia. Mechanistic studies indicated that NZ51 did not cause DDX3 degradation, but greatly diminished its functionality. Moreover, in vivo experiments demonstrated that DDX3 knockdown by shRNA resulted in reduced tumor volume and metastasis without altering tumor vascular volume or permeability-surface area. In initial in vivo experiments, NZ51 treatment did not significantly reduce tumor volume. Further studies are needed to optimize drug formulation, dose and delivery. Continuing work will determine the in vitro-in vivo correlation of NZ51 activity and its utility in a clinical setting.
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