Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.

Autor: Li B; ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA., Cociorva OM, Nomanbhoy T, Weissig H, Li Q, Nakamura K, Liyanage M, Zhang MC, Shih AY, Aban A, Hu Y, Cajica J, Pham L, Kozarich JW, Shreder KR
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Sep 15; Vol. 23 (18), pp. 5217-22. Date of Electronic Publication: 2013 Jul 08.
DOI: 10.1016/j.bmcl.2013.06.087
Abstrakt: As the result of a rhJNK1 HTS, the imidazo[1,2-a]quinoxaline 1 was identified as a 1.6 μM rhJNK1 inhibitor. Optimization of this compound lead to AX13587 (rhJNK1 IC50=160 nM) which was co-crystallized with JNK1 to identify key molecular interactions. Kinase profiling against 125+ kinases revealed AX13587 was an inhibitor of JNK, MAST3, and MAST4 whereas its methylene homolog AX14373 (native JNK1 IC50=47 nM) was a highly specific JNK inhibitor.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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