ArticleJournal of medicinal chemistry2021
Nonpeptidic, Polo-Box Domain-Targeted Inhibitors of PLK1 Block Kinase Activity, Induce Its Degradation and Target-Resistant Cells.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
5 citing papers in PubMed, 15 citations in OpenAlex.
- Structural regulation of PLK1 activity: implications for cell cycle function and drug discovery.Cancer gene therapy · 2025Review
- Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural Basis for Variations in Polo-like Kinase 1 Conformation and Intracellular Stability Induced by ATP-Competitive and Novel Noncompetitive Abbapolin Inhibitors.ACS chemical biology · 2023Article
- Novel Macrocyclic Peptidomimetics Targeting the Polo-Box Domain of Polo-Like Kinase 1.Journal of medicinal chemistry · 2022Article
- Structure-activity and mechanistic studies of non-peptidic inhibitors of the PLK1 polo box domain identified through REPLACE.European journal of medicinal chemistry · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
PLK1, polo-like kinase 1, is a central player regulating mitosis. Inhibition of the subcellular localization and kinase activity of PLK1 through the PBD, polo-box domain, is a viable alternative to ATP-competitive inhibitors, for which the development of resistance and inhibition of related PLK family members are concerns. We describe novel nonpeptidic PBD-binding inhibitors, termed abbapolins, identified through successful application of the REPLACE strategy and demonstrate their potent antiproliferative activity in prostate tumors and other cell lines. Furthermore, abbapolins show PLK1-specific binding and inhibitory activity, as measured by a cellular thermal shift assay and an ability to block phosphorylation of TCTP, a validated target of PLK1-mediated kinase activity. Additional evidence for engagement of PLK1 was obtained through the unique observation that abbapolins induce PLK1 degradation in a manner that closely matches antiproliferative activity. Moreover, abbapolins demonstrate antiproliferative activity in cells that are dramatically resistant to ATP-competitive PLK1 inhibitors.
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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.