Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors

Mario A. Pagano, Giorgia Poletto, Giovanni Di Maira, Giorgio Cozza, Maria Ruzzene, Stefania Sarno, Jenny Bain, Matthew Elliott, Stefano Moro, Giuseppe Zagotto, Flavio Meggio, Lorenzo A Pinna (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    104 Citations (Scopus)

    Abstract

    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 (IC50 values 0.11 and 0.56 µM, respectively), without having any comparable effect on DYRK1 a (IC50 24.5 µM) 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.

    Original languageEnglish
    Pages (from-to)129-139
    Number of pages11
    JournalChemBioChem
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2 Jan 2007

    Keywords

    • Adenosine Triphosphate/chemistry
    • Apoptosis
    • Binding Sites
    • Casein Kinase II/antagonists & inhibitors
    • Cinnamates/pharmacology
    • Dose-Response Relationship, Drug
    • Drug Design
    • Enzyme Inhibitors/pharmacology
    • Humans
    • Inhibitory Concentration 50
    • Jurkat Cells
    • Kinetics
    • Models, Chemical
    • Models, Molecular
    • Molecular Conformation

    Fingerprint

    Dive into the research topics of 'Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors'. Together they form a unique fingerprint.

    Cite this