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Inhibitors of c-Jun N-Terminal Kinase 3

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Proteinkinase Inhibitors

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 36))

Abstract

The serine/threonine kinase c-Jun N-terminal kinase (JNK) 3 is implicated in the pathogenesis of various disorders ranging from neurodegenerative diseases to inflammation, metabolic disease, diabetes, liver diseases, and cancer. Although the number of publications reporting on JNK3 inhibitors has been decreasing in the last few years, this enzyme still constitutes an attractive target. Within the last years, significant progress in the design of JNK3 inhibitors displaying good to excellent selectivity versus other protein kinases has been achieved. However, the development of a JNK-isoform-selective JNK3 inhibitor, which may serve as a tool compound in animal studies to further evaluate the role of JNK3 as a therapeutic target, is highly desirable. This chapter summarizes the progress in the development of reversible and irreversible inhibitors of JNK3.

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Abbreviations

AP:

Activation protein

ATF:

Activating transcription factor

CYP450:

Cytochrome P450

EGFR:

Epidermal growth factor receptor kinase

JNK:

c-Jun N-terminal kinase

MAP:

Mitogen-activated protein

SAPK:

Stress-activated protein kinases

SAR:

Structure-activity relationships

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Acknowledgments

Many thanks to Dr. Francesco Ansideri and Stanislav Andreev for helpful discussions. Dr. Ansideri is also acknowledged for providing Fig. 1. Kristina Schmidt is gratefully acknowledged for proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Tübingen, Germany

    Pierre Koch

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Correspondence to Pierre Koch .

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  1. Eberhard Karls Universität, Pharmazeutisches Institut Eberhard Karls Universität, Tuebingen Center for Academic Drug Discovery (TueCAD2), Tübingen, Germany

    Stefan Laufer

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Koch, P. (2020). Inhibitors of c-Jun N-Terminal Kinase 3. In: Laufer, S. (eds) Proteinkinase Inhibitors. Topics in Medicinal Chemistry, vol 36. Springer, Cham. https://doi.org/10.1007/7355_2020_98

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