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Function, Structure and Topology of Protein Kinases

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Proteinkinase Inhibitors

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

Abstract

Protein kinases represent one of the most successful target classes for the development of new medicines. Because of their key roles in cellular signalling, kinases are stringently regulated by a large diversity of mechanisms such as post-translational modifications, interacting domains and proteins and cellular localization. The high plasticity of protein kinases has been exploited for the development of new inhibitor types such as type-II and type-I½ inhibitors targeting inactive states of the kinase catalytic domain and allosteric inhibitors that target induced binding pockets either adjacent (type-III) or distantly located (type-IV) to the kinase ATP-binding site. Here we discuss structural elements of the kinase active site, key mechanisms of kinase regulation and how these mechanisms can be exploited for the development of selective kinase inhibitors.

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Authors and Affiliations

  1. Johann Wolfgang Goethe-University, Institute for Pharmaceutical Chemistry, Frankfurt, Germany

    Sandra Röhm, Andreas Krämer & Stefan Knapp

  2. Johann Wolfgang Goethe-University, Buchmann Institute for Life Sciences, Frankfurt, Germany

    Sandra Röhm, Andreas Krämer & Stefan Knapp

Authors
  1. Sandra Röhm
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  2. Andreas Krämer
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  3. Stefan Knapp
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Correspondence to Stefan Knapp .

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Editors and Affiliations

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

    Stefan Laufer

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Conflict of interest: The authors have no conflict of interest.

Funding: The authors are grateful for support by the SGC, a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA), Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and Wellcome [106169/ZZ14/Z].

Ethical Approval: This manuscript is a review of previously published accounts, as such no animal or human studies were performed.

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Röhm, S., Krämer, A., Knapp, S. (2020). Function, Structure and Topology of Protein Kinases. In: Laufer, S. (eds) Proteinkinase Inhibitors. Topics in Medicinal Chemistry, vol 36. Springer, Cham. https://doi.org/10.1007/7355_2020_97

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