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Tetrabromocinnamic Acid (TBCA) and Related Compounds Represent a New Class of Specific Protein Kinase CK2 Inhibitors
Author(s) -
Pagano Mario A.,
Poletto Giorgia,
Di Maira Giovanni,
Cozza Giorgio,
Ruzzene Maria,
Sarno Stefania,
Bain Jenny,
Elliott Matthew,
Moro Stefano,
Zagotto Giuseppe,
Meggio Flavio,
Pinna Lorenzo A.
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200600293
Subject(s) - jurkat cells , kinase , chemistry , protein kinase a , biochemistry , potency , protein kinase inhibitor , in vitro , pharmacology , biology , immunology , immune system , t cell
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, DYRK1 a. Here we describe the development of a new class of CK2 inhibitors, conceptually derived from TBB, which have lost their potency toward DYRK1 a. In particular, tetrabromocinnamic acid (TBCA) inhibits CK2 five times more efficiently than TBB (IC 50 values 0.11 and 0.56 μ M , respectively), without having any comparable effect on DYRK1 a (IC 50 24.5 μ 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.