| Literature DB >> 21470862 |
Italo Beria1, Roberto T Bossi, Maria Gabriella Brasca, Michele Caruso, Walter Ceccarelli, Gabriele Fachin, Marina Fasolini, Barbara Forte, Francesco Fiorentini, Enrico Pesenti, Daniele Pezzetta, Helena Posteri, Alessandra Scolaro, Stefania Re Depaolini, Barbara Valsasina.
Abstract
As part of our drug discovery effort, we identified and developed 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. We now report the optimization of this class that led to the identification of NMS-P937, a potent, selective and orally available PLK1 inhibitor. Also, in order to understand the source of PLK1 selectivity, we determined the crystal structure of PLK1 with NMS-P937. The compound was active in vivo in HCT116 xenograft model after oral administration and is presently in Phase I clinical trials evaluation.Entities:
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Year: 2011 PMID： 21470862 DOI： 10.1016/j.bmcl.2011.03.054
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823