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Kinase Inhibitor Specificity and Targeting Human Disease
Author(s) -
English Jessie M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.71.1
Subject(s) - kinome , kinase , small molecule , drug discovery , protein kinase a , computational biology , ask1 , biology , microbiology and biotechnology , bioinformatics , biochemistry , mitogen activated protein kinase kinase
Because of their central role in cell signaling, protein kinases are often co‐opted and aberrantly activated in human disease. The ATP binding site of protein kinases affords an attractive small molecule binding site, but is highly conserved across the kinome. In the last decade protein kinases have been established as attractive therapeutic targets. However, the above two features also present challenges for targeting protein kinases with small molecule inhibitors. Obtaining small molecule inhibitors that are highly selective against the kinome can be difficult, but progress has been made. However dialing in or out desired specificity profiles is still problematic. In addition predicting the implications of kinase inhibition on both efficacy and safety can be difficult due to the pleitropic nature of kinase signaling. Kinase inhibitors currently in clinical trials and on the market vary significantly in their selectivity profiles. This presentation will provide an overview of approaches for identifying selective kinase inhibitors as well as the implications for drug discovery efforts and therapeutic utility of highly selective vs. multikinase inhibitors.