Silmitasertib-sodium-salt-CX-4945-sodium-salt-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESilmitasertib sodium saltCat. No.: HY-50855BCAS No.: 1309357-15-0Synonyms: CX-4945 (sodium salt)分式: CHClNNaO分量: 371.75作靶点: Casein Kinase; Autophagy作通路: Cell Cycle/DNA Damage; Stem Cell/Wnt; Autophagy储存式: Powder -20C 3 years4C 2

2、yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 37.5 mg/mL (100.87 mM; Need ultrasonic)H2O : 16.67 mg/mL (44.84 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6900 mL 13.4499 mL 26.8998 mL5 mM 0.5380 mL 2.6900 mL 5.3800 mL10 mM 0.2690 mL 1.3450 mL 2.6900 mL请根据产品在不

3、同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.72 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolu

4、bility: 2.5 mg/mL (6.72 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Silmitasertib sodium salt种有效、可服、度选择性的 CK2 抑制剂，对 CK2 和 CK2 的 IC50值均为 1 nM。IC50 & Target CK2 CK21 nM (IC50) 1 nM (IC50)体外研究 Silmitasertib (CX-4945) causes cell-cycle arrest and selectivel

5、y induces apoptosis in cancer cells relative tonormal cells, attenuates PI3K/Akt signalingand, and the antiproliferative activity of Silmitasertib (CX-4945) iscorrelated with expression levels of the CK2 catalytic subunit, Attenuation of PI3K/Akt signaling 1.Silmitasertib (CX-4945) with bortezomib t

6、reatment prevents leukemic cells from engaging a functional UPR inorder to buffer the bortezomib-mediated proteotoxic stress in ER lumen, and decreases pro-survival ERchaperon BIP/Grp78 expression 2. Silmitasertib (CX-4945) induces cytotoxicity and apoptosis, and exertsanti-proliferative effects in

7、hematological tumors by downregulating CK2 expression and suppressingactivation of CK2-mediated PI3K/Akt/mTOR signaling pathways 3.体内研究 Silmitasertib (CX-4945) (25 or 75 mg/kg, p.o.) is well tolerated and demonstrated robust antitumor activitywith concomitant reductions of the mechanism-based biomar

8、ker phospho-p21 (T145) in murine xenograftmodels 1.PROTOCOLCell Assay 1 Various cell lines are seeded at a density of 3,000 cells per well 24 hours prior to treatment, in appropriatemedia, and then treated with indicated concentrations of Silmitasertib (CX-4945). Suspensions cells areseeded and trea

9、ted on the same day. Following 4 days of incubation, Alamar Blue (20 L, 10% of volume perwell) is added and the cells are further incubated at 37C for 4-5 hours. Fluorescence with excitationwavelength at 530-560 nm and emission wavelength at 590 nm is measured 1.MCE has not independently confirmed t

10、he accuracy of these methods. They are for reference only.Animal Xenografts are initiated by subcutaneous injection of BxPC-3 cells into the right hind flank region of eachAdministration 1 mouse or BT-474 cells are injected into the mammary fat pad of mice implanted with estrogen pellets. Whentumors

11、 reach a designated volume of 150-200 mm3, animals are randomized and divided into groups of 9 to10 mice per group. Silmitasertib (CX-4945) is administered by oral gavage twice daily at 25 or 75 mg/kg for31 and 35 consecutive days for the BT-474 and BxPC-3 models, respectively. Tumor volumes and bod

12、yweights are measured twice weekly. The length and width of the tumor are measured with calipers and thevolume calculated using the following formula: tumor volume=(length width2)/2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Science. 20

13、17 Dec 1;358(6367).2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Oncogene. 2017 Aug 24;36(34):4943-4950. Oncol Rep. 2017 Feb;37(2):1141-1147. Patent. US20180263995A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Siddiqui

14、-Jain A, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenicsignaling 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-494

15、5 in acute lymphoblastic leukemia: turning offthe prosurvival ER chaperone BIP/Grp78 and turning on the pro-apoptotic NF-B. 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. FrontPharmacol. 2015 Mar 31;6:70.4. Kendall JJ, et al. CK2 blockade causes MPNST cell apoptosis and promotes degradation of -catenin. Oncotarge