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

2009; Elsevier BV; Volume: 19; Issue: 13 Linguagem: Inglês

10.1016/j.bmcl.2009.04.136

1464-3405

David Bebbington, Hayley Binch, Jean‐Damien Charrier, Simon R. L. Everitt, Damien Fraysse, Julian M.C. Golec, David P. Kay, Ronald M. A. Knegtel, Chau Mak, Francesca Mazzei, Andrew T. Miller, Michael Mortimore, Michael A. O’Donnell, Sanjay R. Patel, Françoise Y. T. M. Pierard, Joanne L. Pinder, John R. Pollard, Sharn Ramaya, Daniel P. Robinson, Alistair Rutherford, John Studley, James Westcott,

Neuroblastoma Research and Treatments

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.