ArticleCancer science2019
Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Clinical benefit of ixazomib plus lenalidomide-dexamethasone in myeloma patients with non-canonical NF-κB pathway activation.European journal of haematology · 2020Trial
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Exercise interventions in patients with multiple myeloma: a scoping review.BMC sports science, medicine & rehabilitation · 2025Article
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- FOXO1-regulated lncRNA CYP1B1-AS1 suppresses breast cancer cell proliferation by inhibiting neddylation.Breast cancer research and treatment · 2023Article
- [Differential expression of NEDD8 in different pathological types of chronic rhinosinusitis with nasal polyps].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2023Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- A small molecule inhibitor of the UBE2F-CRL5 axis induces apoptosis and radiosensitization in lung cancer.Signal transduction and targeted therapy · 2022Article
- A review on cullin neddylation and strategies to identify its inhibitors for cancer therapy.3 Biotech · 2022Article
- Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells.International journal of molecular sciences · 2021Article
- A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors.Investigational new drugs · 2021Article
- Targeting NEDDylation as a Novel Approach to Improve the Treatment of Head and Neck Cancer.Cancers · 2021Review
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Article
- Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs.Frontiers in oncology · 2020Review
- Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways.Cancer science · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin proteasome pathway is essential for the proliferation and survival of multiple myeloma (MM) cells. TAS4464, a novel highly potent inhibitor of NEDD8 activating enzyme, selectively inactivates cullin-RING ubiquitin E3 ligases, resulting in accumulation of their substrates. Here, we examined 14 MM cell lines treated with TAS4464. TAS4464 induced growth arrest and cell death in the MM cell lines even in the presence of bone marrow stromal cells. It also induced the accumulation of phospho-inhibitor of κBα and phospho-p100, impaired the activities of nuclear factor κB (NF-κB) transcription factors p65 and RelB, and decreased the expression of NF-κB target genes, suggesting that TAS4464 inhibits both the canonical and non-canonical NF-κB pathways. TAS4464 had similar effects in an in vivo human-MM xenograft mouse model in which it was also observed to have strong antitumor effects. TAS4464 synergistically enhanced the antitumor activities of the standard MM chemotherapies bortezomib, lenalidomide/dexamethasone, daratumumab and elotuzumab. Together, these results suggest that the anti-MM activity of TAS4464 occurs via inhibition of the NF-κB pathways, and that treatment with TAS4464 is a potential approach for treating MM by single and combination therapies.
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