4A4L

CRYSTAL STRUCTURE OF POLO-LIKE KINASE 1 IN COMPLEX WITH A 5-(2-AMINO- PYRIMIDIN-4-YL)-1H-PYRROLE INHIBITOR

Summary for 4A4L

• Entry DOI: 10.2210/pdb4a4l/pdb
• Related: 1Q4K 1Q4O 1UMW 2V5Q 2YAC 4A4O
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PLK1, ZINC ION, L(+)-TARTARIC ACID, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 36337.49

Authors

Bertrand, J.A.,Bossi, R.T. (deposition date: 2011-10-17, release date: 2012-01-11, Last modification date: 2024-05-01)

Primary citation

Caruso, M.,Valsasina, B.,Ballinari, D.,Bertrand, J.A.,Brasca, M.G.,Caldarelli, M.,Cappella, P.,Fiorentini, F.,Gianellini, L.M.,Scolaro, A.,Beria, I.
5-(2-Amino-Pyrimidin-4-Yl)-1H-Pyrrole and 2-(2-Amino-Pyrimidin-4-Yl)-1,5,6,7-Tetrahydro-Pyrrolo[3,2-C]Pyridin-4-One Derivatives as New Classes of Selective and Orally Available Polo-Like Kinase 1 Inhibitors.
Bioorg.Med.Chem.Lett., 22:96-, 2012

PubMed Abstract: The discovery and characterization of two new chemical classes of potent and selective Polo-like kinase 1 (PLK1) inhibitors is reported. For the most interesting compounds, we discuss the biological activities, crystal structures and preliminary pharmacokinetic parameters. The more advanced compounds inhibit PLK1 in the enzymatic assay at the nM level and exhibit good activity in cell proliferation on A2780 cells. Furthermore, these compounds showed high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms. Additionally, the compounds show acceptable oral bioavailability in mice making these inhibitors suitable candidates for further in vivo activity studies.

PubMed: 22154349
DOI: 10.1016/J.BMCL.2011.11.065

Experimental method

X-RAY DIFFRACTION (2.35 Å)