ArticleJournal of medicinal chemistry2020
Re-Evaluating the Mechanism of Action of α,β-Unsaturated Carbonyl DUB Inhibitors b-AP15 and VLX1570: A Paradigmatic Example of Unspecific Protein Cross-linking with Michael Acceptor Motif-Containing Drugs.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Insights into Free Drug Release from EfficaciousACS chemical biology · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30.RSC chemical biology · 2024Article
- A carboxy-terminal ubiquitylation site regulates androgen receptor activity.Communications biology · 2024Article
- Deubiquitinases in Ovarian Cancer: Role in Drug Resistance and Tumor Aggressiveness.International journal of biological sciences · 2024Review
- Preclinical studies of RA475, a guanidine-substituted spirocyclic candidate RPN13/ADRM1 inhibitor for treatment of ovarian cancer.PloS one · 2024Article
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Inhibition of USP14 enhances anti-tumor effect in vemurafenib-resistant melanoma by regulation of Skp2.Cell biology and toxicology · 2023Article
- Strategies for Competitive Activity-Based Protein Profiling in Small Molecule Inhibitor Discovery and Characterization.Israel journal of chemistry · 2023Article
- Identification of galectin-1 and other cellular targets of alpha,beta-unsaturated carbonyl compounds, including dimethylfumarate, by use of click-chemistry probes.Redox biology · 2023Article
- Global Assessment of Drug Target Engagement and Selectivity of Covalent Cysteine-Reactive Inhibitors Using Alkyne-Functionalized Probes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Base-Mediated Nitrophenyl Reductive Cyclization for the Synthesis of Hexahydro-2,6-methano-1-benzazocines.The Journal of organic chemistry · 2022Article
- Comprehensive Target Screening and Cellular Profiling of the Cancer-Active Compound b-AP15 Indicate Abrogation of Protein Homeostasis and Organelle Dysfunction as the Primary Mechanism of Action.Frontiers in oncology · 2022Article
- Flipping the Switch: Innovations in Inducible Probes for Protein Profiling.ACS chemical biology · 2021Review
- Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe.RSC medicinal chemistry · 2021Article
- TTI-101: A competitive inhibitor of STAT3 that spares oxidative phosphorylation and reverses mechanical allodynia in mouse models of neuropathic pain.Biochemical pharmacology · 2021Article
- Sensitivity of Acute Myelocytic Leukemia Cells to the Dienone Compound VLX1570 Is Associated with Inhibition of the Ubiquitin-Proteasome System.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Deubiquitinating enzymes (DUBs) are a growing target class across multiple disease states, with several inhibitors now reported. b-AP15 and VLX1570 are two structurally related USP14/UCH-37 inhibitors. Through a proteomic approach, we demonstrate that these compounds target a diverse range of proteins, resulting in the formation of higher molecular weight (MW) complexes. Activity-based proteome profiling identified CIAPIN1 as a submicromolar covalent target of VLX1570, and further analysis demonstrated that high MW complex formation leads to aggregation of CIAPIN1 in intact cells. Our results suggest that in addition to DUB inhibition, these compounds induce nonspecific protein aggregation, providing molecular explanation for general cellular toxicity.
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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.