4UZH

SAR156497 an exquisitely selective inhibitor of Aurora kinases

Summary for 4UZH

• Entry DOI: 10.2210/pdb4uzh/pdb
• Related: 4UZD
• Descriptor: AURORA 2 KINASE DOMAIN, (4S)-4-(2-fluorophenyl)-2,4,6,7,8,9-hexahydro-5H-pyrazolo[3,4-b][1,7]naphthyridin-5-one (3 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 33626.46

Authors

Pouzieux, S.,Maignan, S.,Crenne, J.Y. (deposition date: 2014-09-05, release date: 2014-11-19, Last modification date: 2024-05-08)

Primary citation

Carry, J.C.,Clerc, F.F.,Minoux, H.,Schio, L.,Mauger, J.,Nair, A.,Parmantier, E.,Le Moigne, R.,Delorme, C.,Nicolas, J.P.,Krick, A.,Abecassis, P.Y.,Crocq-Stuerga, V.,Pouzieux, S.,Delarbre, L.,Maignan, S.,Bertrand, T.,Bjergarde, K.,Ma, N.,Lachaud, S.,Guizani, H.,Lebel, R.,Doerflinger, G.,Monget, S.,Perron, S.,Gasse, F.,Angouillant-Boniface, O.,Filoche-Romme, B.J.,Murer, M.,Gontier, S.,Prevost, C.,Monteiro, M.L.,Combeau, C.
Sar156497 an Exquisitely Selective Inhibitor of Aurora Kinases.
J.Med.Chem., 58:362-, 2015

PubMed Abstract: The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Aurora inhibitors. Indeed, over 10 of them have reached the clinic as potential anticancer therapies. We report herein the discovery and optimization of a novel series of tricyclic molecules that has led to SAR156497, an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy. We also provide insights into its mode of binding to its target proteins, which could explain its selectivity.

PubMed: 25369539
DOI: 10.1021/JM501326K

Experimental method

X-RAY DIFFRACTION (2 Å)