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Protein Tyrosine Kinase Inhibitors as Therapeutic Agents

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Bioorganic Chemistry of Biological Signal Transduction

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 211))

Abstract

Protein tyrosine kinases (PTKs) play a key role in cell signaling and regulate biological processes such as proliferation, differentiation, and apoptosis. The malfunctioning of these proteins is the root of many diseases. Over 60% of all oncoproteins and proto-oncoproteins, which play a key role in cancers, are PTKs. Malfunctioning of PTKs is also the hallmark of other diseases such as psoriasis, Papilloma, Atherosclerosis, pulmonary fibrosis and more. It is therefore logical to target these proteins for drug design aiming at selective and nontoxic drugs. Since the second half of the 1980s we have pioneered and continued to generate tyrosine phosphorylation inhibitors (tyrphostins) as agents against diseases such as cancers, leukemias, lymphomas, psoriasis, restenosis, angiogenesis, and more. Currently, there are already a few tyrphostins in clinical trials. We argue that it is likely that the most effective tyrphostins in the future will be those which target the substrate binding domain of the PTK and not the ATP sub-domain. It is highly likely that tyrphostins against the key PTKs that play a pivotal role in diseases will become an important component in human therapy.

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Authors and Affiliations

  1. Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

    Alexander Levitzki

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  1. Alexander Levitzki
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  1. Max-Planck-Institut für Molekulare Physiologie, Universität Dortmund, Otto-Hahn-Straße 11, 44221, Dortmund, Germany

    Herbert Waldmann

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Levitzki, A. (2000). Protein Tyrosine Kinase Inhibitors as Therapeutic Agents. In: Waldmann, H. (eds) Bioorganic Chemistry of Biological Signal Transduction. Topics in Current Chemistry, vol 211. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-45035-1_1

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  • DOI: https://doi.org/10.1007/3-540-45035-1_1

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