TBB

"目录号: HY-14394

Cell Cycle/DNA DamageStem Cell/Wnt-

TBB 是一种选择性的蛋白激酶 CK2 (CK2)抑制剂，IC50为 1.6 μM。

Casein Kinase

相关产品

LY294002-CX-4945-D4476-DMAT-Emodin-PF-670462-IC261-SR-3029-LH846-TA-01-Ellagic acid-TTP 22-

生物活性

Description

TBB is a selective inhibitor for the protein kinaseCK2withIC50of 1.6 μM.

IC50& Target

IC50: 1.6 μM (CK2), 11.2 μM (GSK3β), 15.6 μM (CDK2)[1]

In Vitro

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 IC50values one-two orders of magnitude higher than CK2 (IC50=0.9 μM). TBB also inhibits endogenous CK2 in cultured Jurkat cells[3].

In Vivo

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].

References

[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.