title: Encountering unpredicted off-target effects of pharmacological inhibitors.
abstract: With the emergence of chemical biology, the use of pharmacological inhibitors in biological research has been expanding. SP600125 is a low-molecular weight compound that has been widely used to inhibit c-Jun-N-terminal kinase (JNK). A recent publication by Tanemura et al. (J. Biochem. 145:345-354, 2009) indicated that SP600125 also inhibits phosphatidylinositol 3-kinase (PI3K) in an isoform-selective fashion: it efficiently inhibited the delta isoform of p110 catalytic subunit (p110δ), which is primarily expressed in leucocytes, but neither of the ubiquitously expressed isoforms, p110α and p110γ. Here, I discuss what we learn from such unpredicted off-target effects of pharmacological inhibitors.
authors.affiliation: Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics*; D008407:Mast Cells / Q000201:enzymology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D016207:Cytokines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017455:Receptors, IgE