2. Academic Validation
  3. Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase

Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase

  • Cancer Res. 2010 Dec 15;70(24):10255-64. doi: 10.1158/0008-5472.CAN-10-2101.
Riccardo Colombo 1,  Marina Caldarelli,  Milena Mennecozzi,  Maria Laura Giorgini,  Francesco Sola,  Paolo Cappella,  Claudia Perrera,  Stefania Re Depaolini,  Luisa Rusconi,  Ulisse Cucchi,  Nilla Avanzi,  Jay Aaron Bertrand,  Roberto Tiberio Bossi,  Enrico Pesenti,  Arturo Galvani,  Antonella Isacchi,  Francesco Colotta,  Daniele Donati,  Jürgen Moll
Affiliations

Affiliation

  • 1 Department of Cell Biology-Oncology, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano 20014, Italy. riccardo.colombo@nervianoms.com
PMID: 21159646 DOI: 10.1158/0008-5472.CAN-10-2101
Abstract

Mps1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. Here we report the identification and characterization of NMS-P715, a selective and orally bioavailable Mps1 small-molecule inhibitor, which selectively reduces Cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical Cancer models. Inhibiting the SAC could represent a promising new approach to selectively target Cancer cells.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12382
    98.41%, MPS1 Inhibitor