ArticleOncology reports2014
Aurora kinase A is a possible target of OSU‑03012 to destabilize MYC family proteins.
Article in Oncology reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma.Frontiers in oncology · 2023Article
- Article
- Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib.Biomolecules · 2021Review
- Tenacigenin B Has Anti-Tumor Effect in Lymphoma by In Vitro and In Vivo Study.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Combined inhibition of Aurora A and p21-activated kinase 1 as a new treatment strategy in breast cancer.Breast cancer research and treatment · 2019Article
- Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1.Gastroenterology · 2019Article
- Cisplatin-resistant cancer cells are sensitive to Aurora kinase A inhibition by alisertib.Molecular oncology · 2017Article
- Origins, genetic landscape, and emerging therapies of small cell lung cancer.Genes & development · 2015Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
OSU-03012, a 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitor, destabilizes MYCN and MYC proteins in neuroblastoma cells. However, AKT phosphorylation is barely detectable in neuroblastoma cells under normal culture conditions whether treated with OSU-03012 or not. This observation suggests that PDK1 is not the main target of OSU-03012 to destabilize MYC and MYCN in neuroblastoma cells. In the present study, we explored one of the possible mechanisms by which OSU-03012 destabilizes MYC and MYCN. Since Aurora kinase A is reported to phosphorylate GSK3β, leading to its inactivation, we hypothesized that one of the targets of OSU-03012 is Aurora kinase A. Comparative analysis of OSU-03012 and VX-680, a potent and specific inhibitor of Aurora kinases, showed that both inhibitors destabilized MYC and MYCN and were significantly growth suppressive to neuroblastoma cell lines. In silico molecular docking analysis further showed that the calculated interaction energy between Aurora kinase A and OSU-03012 was -109.901 kcal/mol, which was lower than that (-89.273 kcal/mol) between Aurora kinase A and FXG, an Aurora kinase-specific inhibitor. Finally, an in vitro Aurora kinase A inhibition assay using a recombinant Aurora kinase A showed that OSU-03012 significantly inhibited Aurora kinase A, although it was weaker in potency than that of VX-680. Thus, OSU-03012 has a likelihood of binding to and inhibiting Aurora kinase A in vivo. These results suggest that OSU-03012 affects multiple cellular targets, including Aurora kinase A, to exhibit its growth suppressive and MYC and MYCN-destabilizing effects on neuroblastoma and other cancer cells.
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Registered trials
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