1. Academic Validation
  2. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo

VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo

  • Nat Med. 2004 Mar;10(3):262-7. doi: 10.1038/nm1003.
Elizabeth A Harrington 1 David Bebbington Jeff Moore Richele K Rasmussen Abi O Ajose-Adeogun Tomoko Nakayama Joanne A Graham Cecile Demur Thierry Hercend Anita Diu-Hercend Michael Su Julian M C Golec Karen M Miller
Affiliations

Affiliation

  • 1 Vertex Pharmaceuticals (Europe) Limited, 88 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK.
Abstract

The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumors, and lead to aneuploidy and tumorigenesis. Here we report the discovery of a highly potent and selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces Apoptosis in a diverse range of human tumor types. This compound causes profound inhibition of tumor growth in a variety of in vivo xenograft models, leading to regression of leukemia, colon and pancreatic tumors at well-tolerated doses. Our data indicate that Aurora Kinase inhibition provides a new approach for the treatment of multiple human malignancies.

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