ArticleCell chemical biology2020
Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- SCaN: A Screening and Characterization Platform for Nanosuspensions Enables In Vivo Delivery of a Crystalline hRpn13ACS pharmacology & translational science · 2026Article
- Exploiting Avidity Effects for the Discovery of Low Affinity Protein-Binding Fragments.Journal of medicinal chemistry · 2025Article
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.Nature communications · 2025Article
- Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.ACS chemical biology · 2025Article
- Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex.Chemical science · 2024Article
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
- Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor.PloS one · 2023Article
- The prognostic value of 19S ATPase proteasome subunits in acute myeloid leukemia and other forms of cancer.Frontiers in medicine · 2023Article
- 19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML).International journal of molecular sciences · 2022Article
- Proteasome substrate receptors and their therapeutic potential.Trends in biochemical sciences · 2022Review
- Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2.FEBS letters · 2022Article
- 26S proteasomes become stably activated upon heat shock when ubiquitination and protein degradation increase.Proceedings of the National Academy of Sciences of the United States of America · 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
- Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma.Nature communications · 2021Article
- Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies.The FEBS journal · 2021Review
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Rpn13 is one of several ubiquitin receptors in the 26S proteasome. Cys88 of Rpn13 has been proposed to be the principal target of RA190, an electrophilic small molecule with interesting anti-cancer activities. Here, we examine the claim that RA190 mediates its cytotoxic effects through engagement with Rpn13. We find no evidence that this is the case. In vitro, RA190 is has no measurable effect on any of the known interactions of Rpn13. In cellulo, we see no physical engagement of Rpn13 by RA190, either on C88 or any other residue. However, chemical proteomics experiments in two different cell lines reveal that dozens of other proteins are heavily engaged by RA190. Finally, increasing or reducing the level of Rpn13 in HeLa and melanoma cells had no effect on the sensitivity of HeLa or melanoma cells to RA190. We conclude that Rpn13 is not the physiologically relevant target of RA190.
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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.