3THB

Structure of PLK1 kinase domain in complex with a benzolactam-derived inhibitor

Summary for 3THB

• Entry DOI: 10.2210/pdb3thb/pdb
• Descriptor: Serine/threonine-protein kinase PLK1, ZINC ION, 9-chloro-2-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thi one (3 entities in total)
• Functional Keywords: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 1
• Total formula weight: 37999.03

Authors

Sintchak, M.D. (deposition date: 2011-08-18, release date: 2011-11-23, Last modification date: 2023-09-13)

Primary citation

Duffey, M.O.,Vos, T.J.,Adams, R.,Alley, J.,Anthony, J.,Barrett, C.,Bharathan, I.,Bowman, D.,Bump, N.J.,Chau, R.,Cullis, C.,Driscoll, D.L.,Elder, A.,Forsyth, N.,Frazer, J.,Guo, J.,Guo, L.,Hyer, M.L.,Janowick, D.,Kulkarni, B.,Lai, S.J.,Lasky, K.,Li, G.,Li, J.,Liao, D.,Little, J.,Peng, B.,Qian, M.G.,Reynolds, D.J.,Rezaei, M.,Scott, M.P.,Sells, T.B.,Shinde, V.,Shi, Q.J.,Sintchak, M.D.,Soucy, F.,Sprott, K.T.,Stroud, S.G.,Nestor, M.,Visiers, I.,Weatherhead, G.,Ye, Y.,D'Amore, N.
Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905).
J.Med.Chem., 55:197-208, 2012

PubMed 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.

PubMed: 22070629
DOI: 10.1021/jm2011172

Experimental method

X-RAY DIFFRACTION (2.5 Å)