| Autor: |
Zhang HC; Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA. hzhang@prdus.jnj.com, Derian CK, McComsey DF, White KB, Ye H, Hecker LR, Li J, Addo MF, Croll D, Eckardt AJ, Smith CE, Li Q, Cheung WM, Conway BR, Emanuel S, Demarest KT, Andrade-Gordon P, Damiano BP, Maryanoff BE |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2005 Mar 24; Vol. 48 (6), pp. 1725-8. |
| DOI: |
10.1021/jm049478u |
| Abstrakt: |
Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-betaII (IC(50) = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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