ArticleScientific reports2016
Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 93 citations in OpenAlex.
- Structure-based screening and identification of a novel Aurora-A-targeting peptide with antiproliferative activity against prostate cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- The ATC12 small molecule inhibits the Aurora-A/TPX2 interaction and impairs the proliferation of breast cancer cells.Cell death & disease · 2026Article
- Learned Conformational Space and Pharmacophore Into Molecular Foundational Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The N-Myc MB0-MBI region interacts specifically and dynamically with the N-lobe of Aurora kinase A.Nature communications · 2026Article
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- Exploring pocket-aware inhibitors of BTK kinase by generative deep learning, molecular docking, and molecular dynamics simulations.RSC advances · 2025Article
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma.Molecular biotechnology · 2024Article
- Selective Aurora A-TPX2 Interaction Inhibitors HaveJournal of medicinal chemistry · 2024Article
- Review
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- Article
- AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation.Life science alliance · 2023Article
- Structural basis for CEP192-mediated regulation of centrosomal AURKA.Science advances · 2023Article
- Aurora Kinase A Regulation by Cysteine Oxidative Modification.Antioxidants (Basel, Switzerland) · 2023Review
- Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.Frontiers in molecular biosciences · 2023Review
- TWN-FS method: A novel fragment screening method for drug discovery.Computational and structural biotechnology journal · 2023Article
- Computational and Biophysical Characterization of Heterocyclic Derivatives of Anthraquinone against Human Aurora Kinase A.ACS omega · 2022Article
- Selective α-Methylation of Aryl Ketones Using Quaternary Ammonium Salts as Solid Methylating Agents.The Journal of organic chemistry · 2022Article
- CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.Cancers · 2022Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The essential mitotic kinase Aurora A (AURKA) is controlled during cell cycle progression via two distinct mechanisms. Following activation loop autophosphorylation early in mitosis when it localizes to centrosomes, AURKA is allosterically activated on the mitotic spindle via binding to the microtubule-associated protein, TPX2. Here, we report the discovery of AurkinA, a novel chemical inhibitor of the AURKA-TPX2 interaction, which acts via an unexpected structural mechanism to inhibit AURKA activity and mitotic localization. In crystal structures, AurkinA binds to a hydrophobic pocket (the 'Y pocket') that normally accommodates a conserved Tyr-Ser-Tyr motif from TPX2, blocking the AURKA-TPX2 interaction. AurkinA binding to the Y- pocket induces structural changes in AURKA that inhibit catalytic activity in vitro and in cells, without affecting ATP binding to the active site, defining a novel mechanism of allosteric inhibition. Consistent with this mechanism, cells exposed to AurkinA mislocalise AURKA from mitotic spindle microtubules. Thus, our findings provide fresh insight into the catalytic mechanism of AURKA, and identify a key structural feature as the target for a new class of dual-mode AURKA inhibitors, with implications for the chemical biology and selective therapeutic targeting of structurally related kinases.
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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.