The selectivity of inhibitors of protein kinase CK2: an update

被引：209

作者：

Pagano, Mario A. ^{[2
,3
,4
]}

Bain, Jenny ^{[5
,6
]}

Kazimierczuk, Zygmunt ^{[1
]}

Sarno, Stefania ^{[2
,3
,4
]}

Ruzzene, Maria ^{[2
,3
,4
]}

Di Maira, Giovanni ^{[2
,3
,4
]}

Elliott, Matthew ^{[5
,6
]}

Orzeszko, Andrzej ^{[7
]}

Cozza, Giorgio ^{[2
,3
]}

Meggio, Flavio ^{[2
,3
]}

Pinna, Lorenzo A. ^{[2
,3
,4
]}

机构：

[1] Polish Acad Sci, Med Res Ctr, Lab Expt Pharmacol, PL-02106 Warsaw, Poland

[2] Univ Padua, Dept Biol Chem, I-35131 Padua, Italy

[3] Univ Padua, Inst Neurosci, CNR, I-35131 Padua, Italy

[4] VIMM, I-35129 Padua, Italy

[5] Univ Dundee, Prot Phosphorylat Unit, Div Signal Transduct Therapy, Dundee DD1 5EH, Scotland

[6] Univ Dundee, Prot Phosphorylat Unit, MRC, Dundee DD1 5EH, Scotland

[7] Mil Univ Technol, PL-00908 Warsaw, Poland

来源：

BIOCHEMICAL JOURNAL | 2008年 / 415卷 / 353-365期

基金：

英国医学研究理事会;

关键词：

ATP mimetics; casein kinase 2 (CK2) inhibitor; drug design; homeodomain-interacting protein kinase 2 (HIPK2); provirus integration site for Moloney murine leukaemia virus 1 (PIM 1); selectivity;

D O I：

10.1042/BJ20080309

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

CK2 (casein kinase 2) is a very pleiotropic serine/threonine protein kinase whose abnormally high constitutive activity has often been correlated to pathological conditions with special reference to neoplasia. The two most widely used cell permeable CK2 inhibitors, TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole), are marketed as quite specific CK2 blockers. In the present study we show, by using a panel of approx. 80 protein kinases, that DMAT and its parent compound TBI (or TBBz; 4,5,6,7-tetrabronio-1H-benzimidazole) are potent inhibitors of several other kinases, with special reference to PIM (provirus integration site for Moloney murine leukaemia virus)1, PIM2, PIM3, PKD1 (protein kinase D1), HIPK2 (homeodomain-interacting protein kinase 2) and DYRK 1a (dual-specificity tyrosine-phosphorylated and -regulated kinase 1a). In contrast, TBB is significantly more selective toward CK2, although it also inhibits PIM1 and PIM3. In an attempt to

引用

页码：353 / 365

页数：13

共 50 条

[1] ERK-8, a new member of the mitogen-activated protein kinase family [J].