Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Tetra-substituted pyridinylimidazoles as dual inhibitors of p38α mitogen-activated protein kinase and c-Jun N-terminal kinase 3 for potential treatment of Huntington’s Disease

Muth, Felix and Günther, Marcel and Bauer, Silke M. and Koch, Pierre and Drueckes, Peter and Koeppler, Juergen and Trappe, Joerg and Laufer, Stefan A. (2015) Tetra-substituted pyridinylimidazoles as dual inhibitors of p38α mitogen-activated protein kinase and c-Jun N-terminal kinase 3 for potential treatment of Huntington’s Disease. Tetra-substituted pyridinylimidazoles as dual inhibitors of p38α mitogen-activated protein kinase and c-Jun N-terminal kinase 3 for potential treatment of Huntington’s Disease, 58 (1). pp. 443-456. ISSN 0022-26231520-4804

Abstract

Tetra-substituted imidazoles were designed as dual inhibitors of c-Jun N-terminal kinases 3 and p38α (mitogen-activated protein) MAP kinase. A library of 39 derivatives was prepared and evaluated in a kinase activity test for their ability to inhibit both kinases, JNK3 and p38α MAP kinase. Dual inhibitors with IC50 values down to the low double-digit nanomolar range at both enzymes were identified. The best balanced dual JNK3/p38α inhibitors being 6g (IC50 JNK3: 18 nM, p38α: 30 nM) and 14d (IC50 JNK3: 26 nM, p38α: 34 nM). They may serve as useful tool compounds for preclinical proof-of-principle studies in order to validate the synergistic role of both kinases in the progression of Huntington’s disease.

Item Type: Article
Keywords: kinase assays,
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/24139

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.