TBB

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TBB is a potent protein kinase CK2 inhibitor, which induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells.|Product information|CAS Number: 17374-26-4|Molecular Weight: 434.71|Formula: C6HBr4N3|Synonym:|Tetrabromobenzotriazole|NSC-231634|TBB|NSC 231634|NSC231634|Chemical Name: 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole|Smiles: BrC1C2N=NNC=2C(Br)=C(Br)C=1Br|InChiKey: OMZYUVOATZSGJY-UHFFFAOYSA-N|InChi: InChI=1S/C6HBr4N3/c7-1-2(8)4(10)6-5(3(1)9)11-13-12-6/h(H,11,12,13)|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: Soluble in DMSO, not in water|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined.|HS Tariff Code: 382200|How to use|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.{{Phenformin} site|{Phenformin} Inhibitor|{Phenformin} Activator|{Phenformin} Protocol|{Phenformin} Data Sheet|{Phenformin} manufacturer} 2 μM).{{Streptonigrin} medchemexpress|{Streptonigrin} Anti-infection|{Streptonigrin} Purity & Documentation|{Streptonigrin} Data Sheet|{Streptonigrin} supplier|{Streptonigrin} Epigenetics} All other kinases tested have IC50 values 50-fold greater than that for CK2.PMID:23614016 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 IC50 values one-two orders of magnitude higher than CK2 (IC50=0.9 μM). TBB also inhibits endogenous CK2 in cultured Jurkat cells.|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).|References:|Gyenis L, Kuś A, Bretner M, Litchfield DW. Functional proteomics strategy for validation of protein kinase inhibitors reveals new targets for a TBB-derived inhibitor of protein kinase CK2. J Proteomics. 2013 Apr 9;81:70-9. doi: 10.1016/j.jprot.2012.09.017. Epub 2012 Sep 25. PubMed PMID: 23017496.Orzechowska E, Kozłowska E, Staroń K, Trzcińska-Danielewicz J. 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. doi: 10.3892/or.2011.1500. Epub 2011 Oct 12. PubMed PMID: 21993828.Isaeva AR, Mitev VI. The protein kinase CK2 inhibitor TBB mediates up-regulation of MEK3/6 and p38δ activities, down-regulation of ERK1/2 activity and induction of G1/S arrest in normal human epidermal autocrine proliferating keratinocytes. J Dermatol Sci. 2011 Aug;63(2):124-6. doi: 10.1016/j.jdermsci.2011.04.005. Epub 2011 Apr 27. PubMed PMID: 21620683.Products are for research use only. Not for human use.|