2. Academic Validation
  3. The discovery of the potent aurora inhibitor MK-0457 (VX-680)

The discovery of the potent aurora inhibitor MK-0457 (VX-680)

  • Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92. doi: 10.1016/j.bmcl.2009.04.136.
David Bebbington 1,  Hayley Binch,  Jean-Damien Charrier,  Simon Everitt,  Damien Fraysse,  Julian Golec,  David Kay,  Ronald Knegtel,  Chau Mak,  Francesca Mazzei,  Andrew Miller,  Michael Mortimore,  Michael O'Donnell,  Sanjay Patel,  Francoise Pierard,  Joanne Pinder,  John Pollard,  Sharn Ramaya,  Daniel Robinson,  Alistair Rutherford,  John Studley,  James Westcott
Affiliations

Affiliation

  • 1 Vertex Pharmaceuticals (Europe) Ltd, 88 Milton Park, Abingdon OX14 4RY, United Kingdom.
PMID: 19447622 DOI: 10.1016/j.bmcl.2009.04.136
Abstract

The identification of a novel series of Aurora Kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) containing the T315I mutation.

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