ArticleCell communication and signaling : CCS2022
Novel dual-targeting c-Myc inhibitor D347-2761 represses myeloma growth via blocking c-Myc/Max heterodimerization and disturbing its stability.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Discovery of Macrocyclic Peptide Inhibitors Targeting MYC Oncoprotein via mRNA Display.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Neurological Effects ofNutrients · 2026Article
- A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression.Molecular oncology · 2026Article
- Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.Biomolecules · 2026Review
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- Novel gene therapy for drug-resistant melanoma: Synergistic combination of PTEN plasmid and BRD4 PROTAC-loaded lipid nanocarriers.Molecular therapy. Nucleic acids · 2024Article
- The total xanthones extracted from Gentianella acuta alleviates HFpEF by activating the IRE1α/Xbp1s pathway.Journal of cellular and molecular medicine · 2024Article
- Design, synthesis, and activity evaluation of 2-iminobenzimidazoles as c-Myc inhibitors for treating multiple myeloma.Heliyon · 2024Article
- The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.Pharmacogenomics and personalized medicine · 2024Review
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid LeukemiaTurkish journal of haematology : official journal of Turkish Society of Haematology · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranscription factor c-Myc plays a critical role in various physiological and pathological events. c-Myc gene rearrangement is closely associated with multiple myeloma (MM) progression and drug resistance. Thereby, targeting c-Myc is expected to be a useful therapeutic strategy for hematological disease, especially in MM.
methodsMolecular docking-based virtual screening and dual-luciferase reporter gene assay were used to identify novel c-Myc inhibitors. Cell viability and flow cytometry were performed for evaluating myeloma cytotoxicity. Western blot, immunofluorescence, immunoprecipitation, GST pull down and Electrophoretic Mobility Shift Assay were performed for protein expression and interaction between c-Myc and Max. c-Myc downstream targets were measured by Q-PCR and Chromatin immunoprecipitation methods. Animal experiments were used to detect myeloma xenograft and infiltration in vivo.
resultsWe successfully identified a novel c-Myc inhibitor D347-2761, which hindered the formation of c-Myc/Max heterodimer and disturbed c-Myc protein stability simultaneously. Compound D347-2761 dose-and time-dependently inhibited myeloma cell proliferation and induced apoptosis. Dual knockout Bak/Bax partially restored D347-2761-mediated cell death. Additionally, compound D347-2761 could, in combination with bortezomib (BTZ), enhance MM cell DNA damage and overcome BTZ drug resistance. Our in vivo studies also showed that compound D347-2761 repressed myeloma growth and distal infiltration by downregulating c-Myc expression. Mechanistically, novel dual-targeting c-Myc inhibitor D347-2761 promoted c-Myc protein degradation via stimulating c-Myc Thr58 phosphorylation levels, which ultimately led to transcriptional repression of CDK4 promoter activity.
conclusionsWe identified a novel dual-targeting c-Myc small molecular inhibitor D347-2761. And this study may provide a solid foundation for developing a novel therapeutic agent targeting c-Myc. Video Abstract.
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