The selectivity of inhibitors of protein kinase CK2: an update
The selectivity of inhibitors of protein kinase CK2: an update
复制标题
DOI：
10.1042/bj20080309
复制
发表时间：
2008-11-01
影响因子：
4.1
通讯作者：
Pinna, Lorenzo A.
中科院分区：
文献类型：
--
作者：
Pagano, Mario A.;Bain, Jenny;Pinna, Lorenzo A.
CK2(酪蛋白激酶2)是一种多效性丝氨酸/苏氨酸蛋白激酶，其异常高的结构活性通常与病理条件有关，特别是与肿瘤的发生有关。两种应用最广泛的细胞通透性CK2抑制剂，4，5，6，7-四溴-1H-苯并三唑和DMAT(2-dimethylamino-4，5，6，7-tetrabromo-1H-benzimidazole)，被作为非常特异的CK2阻滞剂上市。在本研究中，我们通过使用一组大约。80个蛋白激酶，DMAT及其母体化合物TBI(或TBBz；4，5，6，7-四溴-1H-苯并咪唑)是其他几种蛋白激酶的有效抑制剂，特别涉及PIM(Moloney鼠白血病病毒前病毒整合位点)1、PIM2、PIM3、PKD1(蛋白激酶D1)、HIPK2(同源结构域相互作用的蛋白激酶2)和Dyrk 1a(双特异性酪氨酸磷酸化和调节的激酶1a)。相反，TbB对CK2的选择性明显更高，尽管它也抑制PIM1和PIM3。为了试图
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