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Silmitasertib

MCE China：Silmitasertib

Brand：MedChemExpress (MCE)

Cat. No.HY-50855

CAS：1009820-21-6

Synonyms：CX-4945

Purity：99.94%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Silmitasertib (CX-4945) is an orally bioavailable, highly selective and potent CK2 inhibitor, with IC50 values of 1 nM against CK2α and CK2α'.

In Vitro：Silmitasertib (CX-4945) causes cell-cycle arrest and selectively induces apoptosis in cancer cells relative to normal cells, attenuates PI3K/Akt signalingand, and the antiproliferative activity of Silmitasertib (CX-4945) is correlated with expression levels of the CK2α catalytic subunit, Attenuation of PI3K/Akt signaling[1]. Silmitasertib (CX-4945) with PS-341 treatment prevents leukemic cells from engaging a functional UPR in order to buffer the PS-341-mediated proteotoxic stress in ER lumen, and decreases pro-survival ER chaperon BIP/Grp78 expression[2]. Silmitasertib (CX-4945) induces cytotoxicity and apoptosis, and exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways[3].

In Vivo：Silmitasertib (CX-4945) (25 or 75 mg/kg, p.o.) is well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145) in murine xenograft models[1].

Animal Administration：Xenografts are initiated by subcutaneous injection of BxPC-3 cells into the right hind flank region of each mouse or BT-474 cells are injected into the mammary fat pad of mice implanted with estrogen pellets. When tumors reach a designated volume of 150-200 mm3, animals are randomized and divided into groups of 9 to 10 mice per group. Silmitasertib (CX-4945) is administered by oral gavage twice daily at 25 or 75 mg/kg for 31 and 35 consecutive days for the BT-474 and BxPC-3 models, respectively. Tumor volumes and body weights are measured twice weekly. The length and width of the tumor are measured with calipers and the volume calculated using the following formula: tumor volume=(length × width2)/2.

Cell Assay：Various cell lines are seeded at a density of 3,000 cells per well 24 hours prior to treatment, in appropriate media, and then treated with indicated concentrations of Silmitasertib (CX-4945). Suspensions cells are seeded and treated on the same day. Following 4 days of incubation, Alamar Blue (20 μL, 10% of volume per well) is added and the cells are further incubated at 37°C for 4-5 hours. Fluorescence with excitation wavelength at 530-560 nm and emission wavelength at 590 nm is measured.

IC50 & Target：CK2α 1 nM (IC50) CK2α' 1 nM (IC50)

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References：

[1]. Siddiqui-Jain A, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010 Dec 15;70(24):10288-98.  [Content Brief]

[2]. Buontempo F, et al. Synergistic cytotoxic effects of PS-341 and CK2 inhibitor CX-4945 in acute lymphoblastic leukemia: turning off the prosurvival ER chaperone BIP/Grp78 and turning on the pro-apoptotic NF-κB. Oncotarget. 2016 Jan 12;7(2):1323-40.  [Content Brief]

[3]. Chon HJ, et al. The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies. Front Pharmacol. 2015 Mar 31;6:70.  [Content Brief]