1034615-59-2Relevant articles and documents
NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor
Beria, Italo,Bossi, Roberto T.,Brasca, Maria Gabriella,Caruso, Michele,Ceccarelli, Walter,Fachin, Gabriele,Fasolini, Marina,Forte, Barbara,Fiorentini, Francesco,Pesenti, Enrico,Pezzetta, Daniele,Posteri, Helena,Scolaro, Alessandra,Depaolini, Stefania Re,Valsasina, Barbara
, p. 2969 - 2974 (2011)
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.
