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J Med Chem. 2012 Jan 12;55(1):197-208. doi: 10.1021/jm2011172. Epub 2011 Dec 5.

Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905).

Author information

1
Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139, United States. matthew.duffey@mpi.com

Abstract

This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

PMID:
22070629
DOI:
10.1021/jm2011172
[Indexed for MEDLINE]

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