TBB (Synonyms: NSC 231634, Tetrabromobenzotriazole)

TBB is a cell-permeable and ATP-competitive CK2 inhibitor with an IC50 of 0.15 μM for rat liver CK2.
Investigation of the inhibitory power of TBB with a panel of 33 protein kinases shows highest potency for CK2 (casein kinase 2) (human CK2: IC50=1.6 μM at 100 μM ATP). TBB also inhibits three other kinases with less potency: CDK2 (IC50=15.6 μM), phosphorylase kinase (IC50=8.7 μM) and glycogen synthase kinase 3β (GSK3β) (IC50=11.2 μM). All other kinases tested have IC50 values 50-fold greater than that for CK2[1]. The viability of the androgen insensitive PC-3 cells may be diminished by TBB (60 μM TBB) acting either alone or combined with anticancer agents CPT or TRAIL when a proper time schedule of the administration is applied. The time schedule-dependent activity of TBB does not come from its effect on apoptosis in PC-3 cells[2]. TBB is an ATP/GTP competitive inhibitor of protein kinase casein kinase-2 (CK2), has been examined against a panel of 33 protein kinases, either Ser/Thr- or Tyr-specific. In the presence of 10 μM TBB (and 100 μM ATP) only CK2 is drastically inhibited (>85%) whereas three kinases (phosphorylase kinase, glycogen synthase kinase 3L and cyclin-dependent kinase 2/cyclin A) underwent moderate inhibition, with IC50 values one-two orders of magnitude higher than CK2 (IC50=0.9 μM). TBB also inhibits endogenous CK2 in cultured Jurkat cells[3].
The extent of retinal neovascularization in a mouse OIR model is reduced by approximately 60% after treatment with TBB (6 days at 60 mg/kg per day)[4].
Reference:
[1]. De Moliner E, et al. Alternative binding modes of an inhibitor to two different kinases. Eur J Biochem. 2003 Aug;270(15):3174-81.
[2]. Orzechowska E, et al. Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability. Oncol Rep. 2012 Jan;27(1):281-5.
[3]. Sarno S, et al. Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 ('casein kinase-2'). FEBS Lett. 2001 May 4;496(1):44-8.
[4]. Ljubimov AV, et al. Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization. Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4583-91.
[5]. Pagano MA, et al. The selectivity of inhibitors of protein kinase CK2: an update. Biochem J. 2008 Nov 1;415(3):353-65.
[6]. Chen Z, et al. CK2α promotes advanced glycation end products-induced expressions of fibronectin and intercellular adhesion molecule-1 via activating MRTF-A in glomerular mesangial cells. Biochem Pharmacol. 2017 Dec 6;148:41-51.