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Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors by Pierre Raboisson; Oliver Lenz; Tse-I Lin; Dominique Surleraux; Sarvajit Chakravarty; Annick Scholliers; Katrien Vermeiren; Frederic Delouvroy; Thierry Verbinnen; Kenneth Simmen is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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Screening of a focused library of TGF beta kinase inhibitors in the cellular HCV replicon model with luciferase read out yielded a number of low micromolar HCV inhibitors. Medicinal chemistry driven optimization resulted in the discovery of 4-[2-(5bromo-2-fluoro-phenyl)pteridin-4-ylamino]-N-[3-(2-oxopyrrolidin-1-yl)propyl]nicotinamide 36 with a replicon EC 50 of 64 nM, associated with a selective kinase inhibitory profile for human JNK kinases 2 and 3 as well as VEGFR-1, 2, and 3 kinases. Moreover, 36 showed an advantageous PK profile in mice. Experiments performed using different replicon constructs suggest that this series of kinase inhibitors might mediate their effect through the HCV non-structural protein 5A (NS5A).

Who reads Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors?

Author

Pierre Raboisson; Oliver Lenz; Tse-I Lin; Dominique Surleraux; Sarvajit Chakravarty; Annick Scholliers; Katrien Vermeiren; Frederic Delouvroy; Thierry Verbinnen; Kenneth Simmen

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0960-894X)

Published

2007

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)