Cozza Giorgio, Venerando Andrea, Sarno Stefania, Pinna Lorenzo A
Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, Italy.
Biomed Res Int. 2015;2015:734127. doi: 10.1155/2015/734127. Epub 2015 Oct 19.
Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) turned out to be particularly potent (Ki = 0.058 μM) and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX-4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2α) and CK2 holoenzyme (CK2α2 β2), consistent with in silico and in vitro analyses.
据报道，许多多酚类化合物可抑制蛋白激酶，特别是与CK2有关，CK2是一种多效性丝氨酸/苏氨酸激酶，与肿瘤形成、神经退行性疾病和病毒感染有关。然而，一般来说，这些化合物没有严格的选择性。其中，茜素（1,2,5,8-四羟基蒽醌）被证明具有特别强的活性（Ki = 0.058 μM），并且通过在由70种蛋白激酶组成的小样本上进行分析，发现其具有相当高的选择性。在此，通过在由140种激酶组成的更大样本上对茜素进行分析，我们得出结论：茜素是CK2最具选择性的抑制剂之一，优于一流的CK2抑制剂CX-4945，CX-4945目前正在进行癌症治疗的临床试验。此外，我们在此表明，茜素能够区分分离的CK2催化亚基（CK2α）和CK2全酶（CK2α2β2），这与计算机模拟和体外分析结果一致。
