کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1394072 | 984032 | 2008 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Identification of Polyoxometalates as Nanomolar Noncompetitive Inhibitors of Protein Kinase CK2 Identification of Polyoxometalates as Nanomolar Noncompetitive Inhibitors of Protein Kinase CK2](/preview/png/1394072.png)
SummaryProtein kinase CK2 is a multifunctional kinase of medical importance that is dysregulated in many cancers. In this study, polyoxometalates were identified as original CK2 inhibitors. [P2Mo18O62]6− has the most potent activity. It inhibits the kinase in the nanomolar range by targeting key structural elements located outside the ATP- and peptide substrate-binding sites. Several polyoxometalate derivatives exhibit strong inhibitory efficiency, with IC50 values ≤ 10 nM. Furthermore, these inorganic compounds show a striking specificity for CK2 when tested in a panel of 29 kinases. Therefore, polyoxometalates are effective CK2 inhibitors in terms of both efficiency and selectivity and represent nonclassical kinase inhibitors that interact with CK2 in a unique way. This binding mode may provide an exploitable mechanism for developing potent drugs with desirable properties, such as enhanced selectivity relative to ATP-mimetic inhibitors.
Journal: - Volume 15, Issue 7, 21 July 2008, Pages 683–692