DMAT

DMAT is a potent and specific CK2 inhibitor with an IC50 value of 130 nM.

Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase

Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase

Research Areas >> Cancer

CK2:0.13 μM (IC50, Human CK2)

PIM1:0.148 μM (IC50)

PIM2:1.6 μM (IC50)

PIM3:0.097 μM (IC50)

HIPK2:0.37 μM (IC50)

HIPK3:0.59 μM (IC50)

DYRK1a:0.41 μM (IC50)

DYRK2:0.35 μM (IC50)

DYRK3:1.7 μM (IC50)

PKD1:0.18 μM (IC50)

CDK2:0.64 μM (IC50)

DMAT (1 μM-2.5 μM) DMAT is more efficient in killing antiestrogen resistant cells than parental antiestrogen sensitive MCF-7 cells. DMAT-induced cell death of antiestrogen resistant cells is mediated by caspases. DMAT inhibits CK2 activity but the inhibition is similar in the three cell lines, MCF-7, TAMR-1 and 182R-6[1]. DMAT has effects on H295R cell proliferation at concentrations of 10-4 and 10-5mol/Las compared with the control. DMAT (100 μM) significantly increases apoptosis of H295R cells. DMAT (1 nM-1 μM) significantly decreases aldosterone release into supernatants of 72-h H295R cell cultures as compared with the control[2]. DMAT also inhibits PIM1 by a mechanism which is competitive with respect to ATP, and it is a powerful inhibitor of kinases other than CK2[3].

DMAT application in vivo reduces tumor growth in a xenotransplant model by interference with tumor cell proliferation. Biochemical parameters and histology following DMAT administration revealed no alterations in liver tissue[4].

Kinase activity tests are performed in a volume of 50 μL containing (final concentrations): 0.1 μg/μL protein extract, 500 μM CK2 substrate peptide (RRRDDDSDDD), 25 mM Tris-HCl, pH 8.5, 100 μM Na3VO4, 1 mM DTT, 20 mM NaCl, 5 mM MgCl2, 50 μM ATP and appr 1 μCi [γ-32P]-ATP (3000 Ci/mmol). Samples are incubated for 10 min at 30°C. Aliquots are spotted onto P81 phosphocellulose paper and washed 3×5 min in 0.75% phosphoric acid and once in acetone. Incorporation of radiolabelled phosphate is measured by counting the samples in a liquid scintillation counter. Three independent experiments, each done in duplicate, are performed with reproducible results.

H295R cells are plated at a density of 2×104 cells/well into 96-well microplates in complete culture medium and preincubated for 12 h (5% CO2, 37°C, 95% humidity). DMAT in 96% ethanol and Nu-Serum-free culture medium is added to the appropriate wells at final concentrations of 10-4-10-10 M (the highest concentration of ethanol is 1.8% [vol] in the 10-4 M wells). The same volume of Nu-Serum-free culture medium and 96% ethanol is added to the control wells at the same concentration as the solvent in the 10-4 M group. Incubation is performed for 72 h under standard conditions (5% CO2, 37°C, 95% humidity). The absorbance (OD, optical density) of each sample is measured with an enzyme-linked immunosorbent assay (ELISA) microplate reader at a wavelength of 450 nm.

[1]. Yde CW, et al. Induction of cell death in antiestrogen resistant human breast cancer cells by the protein kinase CK2 inhibitorDMAT. Cancer Lett. 2007 Oct 28;256(2):229-37.

[2]. Lawnicka H, et al. Anti-neoplastic effect of protein kinase CK2 inhibitor, 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), on growth and hormonal activity of human adrenocortical carcinoma cell line (H295R) in vitro. Cell Tissue Res. 2010 May;340(

[3]. Pagano MA, et al. The selectivity of inhibitors of protein kinase CK2: an update. Biochem J. 2008 Nov 1;415(3):353-65.

[4]. Sass G, et al. Inhibition of experimental HCC growth in mice by use of the kinase inhibitor DMAT. Int J Oncol. 2011 Aug;39(2):433-42.

Silmitasertib (CX-4945) | D4476 | TBB | Emodin | PF-670462 | SR 3029 | IC 261 | TA-01 | Ellagic acid | TTP 22 | LH846 | Casein Kinase II Inhibitor IV | PF 4800567