4,5,6,7-四溴-1H-苯并三唑

Investigation of the inhibitory power of TBB with a panel of 33 protein kinases shows highest potency for CK2 (casein kinase 2) (human CK2: IC ₅₀ =1.6 μM at 100 μM ATP). TBB also inhibits three other kinases with less potency: CDK2 (IC ₅₀ =15.6 μM), phosphorylase kinase (IC ₅₀ =8.7 μM) and glycogen synthase kinase 3β (GSK3β) (IC ₅₀ =11.2 μM). All other kinases tested have IC50 values 50-fold greater than that for CK2. 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. 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 IC ₅₀ values one-two orders of magnitude higher than CK2 (IC ₅₀ =0.9 μM). TBB also inhibits endogenous CK2 in cultured Jurkat cells.

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).