Special Issue "Protein Kinase Inhibitors"

Guest Editor
Prof. Dr. Lee M. Graves
Department of Pharmacology, University of NC at Chapel Hill, Chapel Hill, NC, Room 4111, Genetic Medicine Building, CB# 7365120 Mason Farm Road, Chapel Hill, NC, 27599-7365, USA
E-Mail:
Phone: +1 919 966 0915

Submission

All manuscripts should be submitted to pharmaceuticals@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.

• p38 MAP kinase
• Erk
• Jnk
• Raf
• BCR-Abl,p70 S6 kinase
• mTor
• Pyk2

Type of Paper: Review
Title: Protein and Lipid Kinase Inhibitors as Treatment Modalities: Potential and Limitation
Author: Doriano Fabbro
Affiliation: Center for Proteomic Chemistry, Head of Kinase Biology, Expertise Platform Kinases, WSJ-152.1.72.1, Fabrikstrasse 16, CH-4056 Basel, Switzerland; E-Mail: doriano.fabbro@novartis.com
Abstract: Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions. Deregulation of these kinase activities lead to a variety of pathologies ranging from cancer, inflammatory diseases, diabetes, infectious diseases, cardiovascular disorders, cell growth and survival. 518 protein kinases and about 20 lipid modifying kinases are encoded by the human genome and a much larger proportion of additional kinases are present in parasites, bacterial, fungal and viral genomes that are susceptible to exploitation as drug targets. Since many human diseases result from over-activation of protein and lipid kinases due to mutations and/or over-expression, these enzyme class represent an important target for the pharmaceutical industry. Approximately one third of all protein targets under investigation in the pharmaceutical industry are protein and lipid kinases, The kinase inhibitors that have been launched, thus far, are mainly in oncology indications and are directed against an handful of protein and lipid kinases. With one exception, all of these registered kinase inhibitors are directed towards the ATP-site and display different selectivities, potencies and pharmacokinetic properties. At present about 150 kinase-targeted drugs are in clinical development and many more in various stages of pre-clinical development. Kinase inhibitor drugs which are in clinical trials, target all stages of signal transduction from the receptor protein tyrosine kinases that initiate intracellular signaling, through second-messenger dependent lipid and protein kinases and protein kinases that regulate the cell cycle. This review will provide an insight into protein and lipid kinase drug discovery with respect to achievements, binding modes of inhibitors and novel avenues for the generation of second generation kinase inhibitors to treat cancers and other indications.