ArticleScientific reports2016
The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06536413 (Phase IB/II Study Combining All-Trans Retinoic Acid), which is not on this map. Cited by 97 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Phase IB/II Study Combining All-Trans Retinoic Acid (ATRA) With Carfilzomib Based Therapy in Plasma Cell Myeloma Patients Refractory to Carfilzomib
Who cites it
97 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.Frontiers in physiology · 2020Pooled it
- Positive cytoplasmic UCHL5 tumor expression in gastric cancer is linked to improved prognosis.PloS one · 2018Trial
- Proteomic profiling revealed unique disease biology associated with 1q abnormalities in multiple myeloma.NPJ precision oncology · 2026Article
- VLX1570 suppresses neuroblastoma growth through inhibition of PCNA-associated proliferative signaling and potentiates cisplatin antitumor activity.Frontiers in pharmacology · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Proteostasis signatures in human diseases.PLoS computational biology · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- Ubiquitin: Not just a one-way ticket to the proteasome, but a therapeutic dial to fine-tune the molecular landscape of disease.Clinical and translational medicine · 2024Review
- Article
- Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.bioRxiv : the preprint server for biology · 2024Article
- Covalent Targeting As a Common Mechanism for Inhibiting NLRP3 Inflammasome Assembly.ACS chemical biology · 2024Article
- A carboxy-terminal ubiquitylation site regulates androgen receptor activity.Communications biology · 2024Article
- The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.Frontiers in immunology · 2024Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Exposure of multiple myeloma cells to VLX1570 resulted in thermostabilization of USP14 at therapeutically relevant concentrations. Transient knockdown of USP14 or UCHL5 expression by electroporation of siRNA reduced the viability of multiple myeloma cells. Treatment of multiple myeloma cells with VLX1570 induced the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. Sensitivity to VLX1570 was moderately affected by altered drug uptake, but was unaffected by overexpression of BCL2-family proteins or inhibitors of caspase activity. Finally, treatment with VLX1570 was found to lead to extended survival in xenograft models of multiple myeloma. Our findings demonstrate promising antiproliferative activity of VLX1570 in multiple myeloma, primarily associated with inhibition of USP14 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.