2J50

Structure of Aurora-2 in complex with PHA-739358

Summary for 2J50

• Entry DOI: 10.2210/pdb2j50/pdb
• Related: 1MQ4 1MUO 1OL5 1OL6 1OL7 2BMC 2C6D 2C6E 2J4Z
• Descriptor: SERINE/THREONINE-PROTEIN KINASE 6, N-[(3E)-5-[(2R)-2-METHOXY-2-PHENYLACETYL]PYRROLO[3,4-C]PYRAZOL-3(5H)-YLIDENE]-4-(4-METHYLPIPERAZIN-1-YL)BENZAMIDE, SULFATE ION (3 entities in total)
• Functional Keywords: transferase, phosphorylation, nucleotide-binding, kinase, cell cycle, atp-binding, nucleotide- binding, serine/threonine-protein kinase, serine-threonine-protein kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 65879.39

Authors

Cameron, A.D.,Izzo, G.,Storici, P.,Rusconi, L.,Fancelli, D.,Varasi, M.,Berta, D.,Bindi, S.,Forte, B.,Severino, D.,Tonani, R.,Vianello, P. (deposition date: 2006-09-08, release date: 2006-11-06, Last modification date: 2024-05-08)

Primary citation

Fancelli, D.,Moll, J.,Varasi, M.,Bravo, R.,Artico, R.,Berta, D.,Bindi, S.,Cameron, A.D.,Candiani, I.,Cappella, P.,Carpinelli, P.,Croci, W.,Forte, B.,Giorgini, M.L.,Klapwijk, J.,Marsiglio, A.,Pesenti, E.,Rocchetti, M.,Roletto, F.,Severino, D.,Soncini, C.,Storici, P.,Tonani, R.,Zugnoni, P.,Vianello, P.
1,4,5,6-Tetrahydropyrrolo[3,4-C]Pyrazoles: Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile.
J.Med.Chem., 49:7247-, 2006

PubMed Abstract: The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.

PubMed: 17125279
DOI: 10.1021/JM060897W

Experimental method

X-RAY DIFFRACTION (3 Å)