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CX-4945 sodium salt

CAS# 1309357-15-0

CX-4945 sodium salt

Catalog No. BCC5586----Order now to get a substantial discount!

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Chemical structure

CX-4945 sodium salt

3D structure

Chemical Properties of CX-4945 sodium salt

Cas No. 1309357-15-0 SDF Download SDF
PubChem ID 49788959 Appearance Powder
Formula C19H11ClN3NaO2 M.Wt 371.75
Type of Compound N/A Storage Desiccate at -20°C
Synonyms Silmitasertib sodium salt
Solubility H2O : 16.67 mg/mL (44.84 mM; Need ultrasonic)
DMSO : 6.67 mg/mL (17.94 mM; Need ultrasonic)
Chemical Name sodium;5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylate
SMILES C1=CC(=CC(=C1)Cl)NC2=C3C=CN=CC3=C4C=CC(=CC4=N2)C(=O)[O-].[Na+]
Standard InChIKey ODDAAPQSODILSN-UHFFFAOYSA-M
Standard InChI InChI=1S/C19H12ClN3O2.Na/c20-12-2-1-3-13(9-12)22-18-15-6-7-21-10-16(15)14-5-4-11(19(24)25)8-17(14)23-18;/h1-10H,(H,22,23)(H,24,25);/q;+1/p-1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Protocol

Kinase Assay [1]
The percent inhibition of each kinase is estimated using 0.5 μM CX-4945 at ATP concentrations equivalent to the Km value for ATP for each respective human recombinant kinase. The determination of IC50 values is done at ATP concentrations equivalent to the Km for ATP for each kinase using 9 concentrations of CX-4945 over a range of 0.0001 to 1 μM. The Ki value (inhibition constant) for CX-4945 against recombinant CK2 is determined by graphing the IC50 values of CX-4945 determined in the presence of various concentrations of ATP against the concentration of ATP.

Cell Assay [1]
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 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[1].

Animal Administration [1]
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. 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.

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. [2]. Buontempo F, et al. Synergistic cytotoxic effects of bortezomib 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. [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. [4]. Kendall JJ, et al. CK2 blockade causes MPNST cell apoptosis and promotes degradation of β-catenin. Oncotarget. 2016 Aug 16;7(33):53191-53203.

CX-4945 sodium salt Dilution Calculator

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CX-4945 sodium salt Molarity Calculator

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Preparing Stock Solutions of CX-4945 sodium salt

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.69 mL 13.4499 mL 26.8998 mL 53.7996 mL 67.2495 mL
5 mM 0.538 mL 2.69 mL 5.38 mL 10.7599 mL 13.4499 mL
10 mM 0.269 mL 1.345 mL 2.69 mL 5.38 mL 6.7249 mL
50 mM 0.0538 mL 0.269 mL 0.538 mL 1.076 mL 1.345 mL
100 mM 0.0269 mL 0.1345 mL 0.269 mL 0.538 mL 0.6725 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on CX-4945 sodium salt

CX-4945 sodium salt is an orally bioavailable, highly selective and potent CK2 inhibitor, with IC50 values of 1 nM against CK2α and CK2α'.

In Vitro: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 CX-4945 is correlated with expression levels of the CK2α catalytic subunit, Attenuation of PI3K/Akt signaling[1]. CX-4945 with bortezomib treatment prevents leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen, and decreases pro-survival ER chaperon BIP/Grp78 expression[2]. 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: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].

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. [2]. Buontempo F, et al. Synergistic cytotoxic effects of bortezomib 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. [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. [4]. Kendall JJ, et al. CK2 blockade causes MPNST cell apoptosis and promotes degradation of β-catenin. Oncotarget. 2016 Aug 16;7(33):53191-53203.

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Description

Silmitasertib sodium salt is an orally bioavailable, highly selective and potent CK2 inhibitor, with IC50 values of 1 nM against CK2α and CK2α'.

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