2YAC

Crystal structure of Polo-like kinase 1 in complex with NMS-P937

Summary for 2YAC

• Entry DOI: 10.2210/pdb2yac/pdb
• Related: 1Q4K 1Q4O 1UMW 2V5Q
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PLK1, 1-(2-HYDROXYETHYL)-8-[[5-(4-METHYLPIPERAZIN-1-YL)-2-(TRIFLUOROMETHOXY)PHENYL]AMINO]-4,5-DIHYDROPYRIMIDO[5,4-G]INDAZOLE-3-CARBOXAMIDE, ZINC ION, ... (5 entities in total)
• Functional Keywords: transferase, atp-binding, cell cycle, cell division, mitosis, nucleotide-binding, nucleus
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 36394.54

Authors

Bertrand, J.A.,Bossi, R.T. (deposition date: 2011-02-18, release date: 2011-04-06, Last modification date: 2024-05-01)

Primary citation

Beria, I.,Bossi, R.T.,Brasca, M.G.,Caruso, M.,Ceccarelli, W.,Fachin, G.,Fasolini, M.,Forte, B.,Fiorentini, F.,Pesenti, E.,Pezzetta, D.,Posteri, H.,Scolaro, A.,Depaolini, S.R.,Valsasina, B.
Nms-P937, a 4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline Derivative as Potent and Selective Polo-Like Kinase 1 Inhibitor.
Bioorg.Med.Chem.Lett., 21:2969-, 2011

PubMed 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.

PubMed: 21470862
DOI: 10.1016/J.BMCL.2011.03.054

Experimental method

X-RAY DIFFRACTION (2.2 Å)