| Structural highlights
Publication Abstract from PubMed
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, several 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-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.
SAR156497 an exquisitely selective inhibitor of Aurora kinases.,Carry JC, Clerc FF, Minoux H, Schio L, Mauger J, Nair A, Parmantier E, Le Moigne R, Delorme C, Nicolas JP, Krick A, Abecassis PY, 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 BJ, Murer M, Gontier S, Prevost C, Monteiro ML, Combeau C J Med Chem. 2014 Nov 4. PMID:25369539[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Carry JC, Clerc FF, Minoux H, Schio L, Mauger J, Nair A, Parmantier E, Le Moigne R, Delorme C, Nicolas JP, Krick A, Abecassis PY, 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 BJ, Murer M, Gontier S, Prevost C, Monteiro ML, Combeau C. SAR156497 an exquisitely selective inhibitor of Aurora kinases. J Med Chem. 2014 Nov 4. PMID:25369539 doi:https://dx.doi.org/10.1021/jm501326k
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