ArticleCell death & disease2018
The binding landscape of a partially-selective isopeptidase inhibitor with potent pro-death activity, based on the bis(arylidene)cyclohexanone scaffold.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- NSC632839 suppresses esophageal squamous cell carcinoma cell proliferation in vitro by triggering spindle assembly checkpoint-mediated mitotic arrest and CREB-Noxa-dependent apoptosis.Cancer cell international · 2025Article
- Identification and evaluation of antiviral activity of novel compounds targeting SARS-CoV-2 virus by enzymatic and antiviral assays, and computational analysis.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells.Pharmaceutics · 2024Article
- A carboxy-terminal ubiquitylation site regulates androgen receptor activity.Communications biology · 2024Article
- Nanomechanical Characterization of Ovarian Cancer Cell Lines as a Marker of Response to 2c Treatment.International journal of molecular sciences · 2023Article
- Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency.Cell death discovery · 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
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- Induction of ER Stress in Acute Lymphoblastic Leukemia Cells by the Deubiquitinase Inhibitor VLX1570.International journal of molecular sciences · 2020Article
- GSK3β is a key regulator of the ROS-dependent necrotic death induced by the quinone DMNQ.Cell death & disease · 2020Article
- Analysis of determinants for in vitro resistance to the small molecule deubiquitinase inhibitor b-AP15.PloS one · 2019Article
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Authors and funding
10 authors.
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Abstract
Diaryldienone derivatives with accessible β-carbons show strong anti-neoplastic properties, related to their ability to make covalent adducts with free thiols by Michael addition, and low toxicity in vivo. Accumulation of poly-ubiquitylated proteins, activation of the unfolded protein response (UPR) and induction of cell death are universal hallmarks of their activities. These compounds have been characterized as inhibitors of isopeptidases, a family of cysteine-proteases, which de-conjugate ubiquitin and ubiquitin-like proteins from their targets. However, it is unclear whether they can also react with additional proteins. In this work, we utilized the biotin-conjugated diaryldienone-derivative named 2c, as a bait to purify novel cellular targets of these small molecules. Proteomic analyses have unveiled that, in addition to isopeptidases, these inhibitors can form stable covalent adducts with different intracellular proteins, thus potentially impacting on multiple functions of the cells, from cytoskeletal organization to metabolism. These widespread activities can explain the ability of diaryldienone derivatives to efficiently trigger different cell death pathways.
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