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
  • 1. Department of Cell Biology-Oncology, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano 20014, Italy. [email protected]
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.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12382
    NMS-P715
    99.30%, MPS1 Inhibitor
    target: Mps1
    Research Areas: Cancer