ArticleCell chemical biology2020
Mechanistic Studies of the Multiple Myeloma and Melanoma Cell-Selective Toxicity of the Rpn13-Binding Peptoid KDT-11.
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 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- NMR-Guided Studies to Establish the Binding Interaction between a Peptoid and Protein.Journal of the American Chemical Society · 2025Article
- Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling.Experimental hematology & oncology · 2023Article
- Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma.Nature communications · 2021Article
- Article
- Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies.The FEBS journal · 2021Review
- Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190.Cell chemical biology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported a peptoid ligand for the proteasomal ubiquitin receptor Rpn13 called KDT-11 and demonstrated that this compound is toxic to multiple myeloma cells, but not non-malignant cells. Here, we show that KDT-11 decreases the viability of a variety of cancer cell lines, especially melanomas and various blood cancers. The peptoid induces selective G1 cell-cycle arrest, resulting in eventual apoptosis. While KDT-11 does not antagonize any of the known protein-protein interactions involving Rpn13, the peptoid inhibits the ability of Rpn13 to stimulate the activity of an associated deubiquitylase Uch37/UCHL5 in vitro, suggesting a high level of Uch37 activity might be important for cancer cell proliferation. However, a variety of experiments in SK-MEL-5 melanoma cells suggest that KDT-11's cytotoxic effects are mediated by interactions with proteins other than Rpn13.
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