Literature DB >> 15196000

The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity.

Emile van den Akker1, Thamar B van Dijk, Uwe Schmidt, Lamberto Felida, Hartmut Beug, Bob Löwenberg, Marieke von Lindern.   

Abstract

LFM-A13, or alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)propenamide, was shown to inhibit Bruton's tyrosine kinase (Btk). Here we show that LFM-A13 efficiently inhibits erythropoietin (Epo)-induced phosphorylation of the erythropoietin receptor, Janus kinase 2 (Jak2) and downstream signalling molecules. However, the tyrosine kinase activity of immunoprecipitated or in vitro translated Btk and Jak2 was equally inhibited by LFM-A13 in in vitro kinase assays. Finally, Epo-induced signal transduction was also inhibited in cells lacking Btk. Taken together, we conclude that LFM-A13 is a potent inhibitor of Jak2 and cannot be used as a specific tyrosine kinase inhibitor to study the role of Btk in Jak2-dependent cytokine signalling.

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Year:  2004        PMID: 15196000     DOI: 10.1515/BC.2004.045

Source DB:  PubMed          Journal:  Biol Chem        ISSN: 1431-6730            Impact factor:   3.915


  11 in total

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3.  Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening.

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Journal:  Bioorg Med Chem Lett       Date:  2009-05-05       Impact factor: 2.823

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5.  Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells.

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Journal:  J Immunol       Date:  2009-01-01       Impact factor: 5.422

6.  Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo.

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Journal:  PLoS One       Date:  2016-01-19       Impact factor: 3.240

8.  Simultaneous use of erythropoietin and LFM-A13 as a new therapeutic approach for colorectal cancer.

Authors:  Anna Tankiewicz-Kwedlo; Justyna Magdalena Hermanowicz; Tomasz Domaniewski; Krystyna Pawlak; Małgorzata Rusak; Anna Pryczynicz; Arkadiusz Surazynski; Tomasz Kaminski; Adam Kazberuk; Dariusz Pawlak
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9.  Alternatively activated macrophage-derived RELM-{alpha} is a negative regulator of type 2 inflammation in the lung.

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Journal:  J Exp Med       Date:  2009-04-06       Impact factor: 14.307

10.  Erythropoietin Intensifies the Proapoptotic Activity of LFM-A13 in Cells and in a Mouse Model of Colorectal Cancer.

Authors:  Anna Tankiewicz-Kwedlo; Justyna Magdalena Hermanowicz; Krystyna Pawlak; Robert Czarnomysy; Krzysztof Bielawski; Izabela Prokop; Dariusz Pawlak
Journal:  Int J Mol Sci       Date:  2018-04-23       Impact factor: 5.923

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