Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors
Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors
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DOI：
10.1002/cbic.200600293
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发表时间：
2007-01-02
期刊：
影响因子：
3.2
通讯作者：
Pinna, Lorenzo A.
中科院分区：
文献类型：
--
作者：
Pagano, Mario A.;Poletto, Giorgia;Pinna, Lorenzo A.
蛋白激酶CK2的异常高组成活性，其水平在各种肿瘤中升高，被怀疑是其致病潜力的基础。最广泛使用的CK2抑制剂是4,5,6,7-四溴苯并三唑（TBB），它对另一种激酶DYRK1a具有相当的疗效。在这里，我们描述了一类新的CK2抑制剂的发展，概念上源于TBB，它已经失去了对DYRK1a的效力。特别是，四溴肉桂酸（TBCA）抑制CK2的效率是TBB的5倍（IC50值分别为0.11和0.56 μ m），而对DYRK1a （IC50值为24.5 μ m）或28种蛋白激酶没有任何类似的作用。TBCA对细胞研究的有用性已经得到验证，表明它比TBB更有效地通过增强凋亡来降低Jurkat细胞的活力。总的来说，报告的数据支持这样一种观点，即适当衍生化的四溴苯分子可能为解剖CK2的细胞功能和抵消其致病潜力提供强有力的试剂。
Abnormally high constitutive activity of protein kinase CK2, levels of which are elevated in a variety of tumours, is suspected to underlie its pathogenic potential. The most widely employed CK2 inhibitor is 4,5,6,7-tetrabromobenzotriazole (TBB), which exhibits a comparable efficacy toward another kinase, DYRK1a. Here we describe the development of a new class of CK2 inhibitors, conceptually derived from TBB, which hove lost their potency toward DYRK1a. In particular, tetrabromocinnamic acid (TBCA) inhibits CK2 five times more efficiently than TBB (IC50 values 0.11 and 0.56 mu m, respectively), without having any comparable effect on DYRK1a (IC50 24.5 mu m) or on a panel of 28 protein kinases. The usefulness of TBCA for cellular studies has been validated by showing that it reduces the viability of Jurkat cells more efficiently than TBB through enhancement of Apoptosis. Collectively taken, the reported data support the view that suitably derivatized tetrabromobenzene molecules may provide powerful reagents for dissecting the cellular functions of CK2 and counteracting its pathogenic potentials.