2. Academic Validation
  3. The ATC12 small molecule inhibits the Aurora-A/TPX2 interaction and impairs the proliferation of breast cancer cells

The ATC12 small molecule inhibits the Aurora-A/TPX2 interaction and impairs the proliferation of breast cancer cells

  • Cell Death Dis. 2026 Mar 24;17(1):356. doi: 10.1038/s41419-026-08579-3.
Dalila Boi # 1,  Giulia Fianco # 1,  Federica Polverino 1,  Francesco Fiorentino 2,  Anna Mastrangelo 1,  Simone Rossi 2,  Elisabetta Rubini 2,  Serena Rosignoli 3,  Francesca Troilo 1,  Maria Rosaria Antonelli 1,  Dalila Tarquini 1,  Laura Cervoni 2,  Serena Rinaldo 2,  Angela Tramonti 1,  Eleonora Kristina Scarpone 4,  Chiara Naro 4 5,  Claudio Sette 4 5,  Venturina Stagni 1 6,  Gianni Colotti 1,  Dante Rotili 7 8,  Alessandro Paiardini 9,  Giulia Guarguaglini 10,  Italia Anna Asteriti 11
Affiliations

Affiliations

  • 1 Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Rome, Italy.
  • 2 Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
  • 3 Centre for Regenerative Medicine "Stefano Ferrari", Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 4 GSTeP-Organoids Research Core Facility, IRCCS Fondazione Policlinico A. Gemelli, Rome, Italy.
  • 5 Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, Rome, Italy.
  • 6 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Signal transduction Unit, Rome, Italy.
  • 7 Department of Science, Roma Tre University, Rome, Italy.
  • 8 Biostructures and Biosystems National Institute (INBB), Rome, Italy.
  • 9 Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy. [email protected].
  • 10 Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Rome, Italy. [email protected].
  • 11 Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Rome, Italy. [email protected].
  • # Contributed equally.
PMID: 41876446 DOI: 10.1038/s41419-026-08579-3
Abstract

The Aurora-A kinase and its major regulator TPX2 act as key players during Mitosis. Both are overexpressed in tumors, and the Aurora-A/TPX2 complex has been proposed as a potential oncogenic holoenzyme. Evidence of Aurora-A non-mitotic roles in Cancer, some of which depend on its nuclear accumulation in interphase and are independent from the kinase activity, is emerging. Indeed, many Aurora-A ATP-competitive inhibitors have shown limited efficacy in clinical trials so far, highlighting the need for novel strategies to inhibit Aurora-A. Interestingly, our recent results suggest an involvement of TPX2 also in the non-mitotic protumorigenic roles of Aurora-A, which makes the Aurora-A/TPX2 complex a promising target. We previously described Aurora-A/TPX2 protein-protein interaction inhibitors. Here, starting from in silico analyses, we identified a new compound, i.e., ATC12, which we validated in vitro as a molecule able to bind Aurora-A and to compete with TPX2. We investigated the effects of ATC12 in 2D cultures and 3D mammospheres of breast Cancer cell lines, as well as in patient-derived organoids, and observed an impairment of Aurora-A/TPX2 interaction and a decrease in cell viability and proliferation. Altogether, our observations support the targeting of the Aurora-A/TPX2 complex as a promising strategy for the development of novel anti-cancer therapeutics.

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