CX-4945 (Silmitasertib)
(Synonyms: CX 4945;CX4945) 目录号 : GC13037
A potent, orally bioavailable CK2 inhibitor
Cas No.:1009820-21-6
Sample solution is provided at 25 µL, 10mM.
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CX-4945 (Silmitasertib) is a potent and selective casein kinase 2 (CK2) inhibitor with IC50 value of 1 nM. It is ATP-competitive and can be taken orally [1].
CX-4945 has been reported to have antiproliferative activity against a wide range of tumor cell lines. It is suggested that CX-4945 suppresses the CK2 regulated PI3K/Akt signaling pathway by inhibiting Akt phosphorylation at Serine 129, but not by activating PTEN. Additionally, cells treated with CX-4945 had a reduction of p21 phophorylation and an up-regulations of total p21 and p27. CX-4945 has been shown to induce cell-cycle arrest at G2/M phase in breast cancer cell line BT-474. It also causes cell-cycle arrest at G1 phase the breast cancer cell line BxPC-3) [1].
In CX-4945 and BxPC-3 derived mouse xenograft model, CX-4945 induced a reduction of phos-p21 expression along with anti-carcinoma effects [1]
References:
[1] Siddiqui-Jain A1, Drygin D, Streiner N, Chua P, Pierre F, O'Brien SE, Bliesath J, Omori M, Huser N, Ho C, Proffitt C, Schwaebe MK, Ryckman DM, Rice WG,Anderes K. 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.
| Cell experiment [1]: | |
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Cell lines |
Jurkat cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
4d; IC50=0.1 μM |
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Applications |
CK2 inhibition was confirmed by measuring the phosphorylation level of the CK2 specific phosphorylation site on Akt (S129). CX-4945 induced dephosphorylation of Akt (S129) and a rapid dephosphorylation of the Akt substrate p21 (T145). Apoptosis was induced by CX-4945. CX-4945 was also found to potently inhibit endogenous intracellular CK2 activity with an IC50 of 0.1 μM in Jurkat cells. |
| Animal experiment [1]: | |
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Animal models |
Athymic mice |
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Dosage form |
75 mg/kg; bid; oral taken |
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Applications |
CX-4945 was tested for in vivo efficacy in established human prostate PC3 xenograft model in athymic mice. Mice bearing subcutaneous PC3 tumors were treated with CX-4945 (25 mg/kg, 50 mg/kg, and 75 mg/kg, p.o, bid). CX-4945 demonstrated tumor growth inhibition (TGI = 19%, 40%, and 86%, respectively) compared to vehicle treated control, and a dose responsive efficacy was observed. Last, CX-4945 was well tolerated in mice as assessed by minimal changes in body weight during the course of treatment compared to vehicle control. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Pierre F, Chua P C, O’Brien S E, et al. Discovery and SAR of 5-(3-chlorophenylamino) benzo [c][2, 6] naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer[J]. Journal of medicinal chemistry, 2010, 54(2): 635-654. | |
| Cas No. | 1009820-21-6 | SDF | |
| 别名 | CX 4945;CX4945 | ||
| 化学名 | 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid | ||
| Canonical SMILES | C1=CC(=CC(=C1)Cl)NC2=C3C=CN=CC3=C4C=CC(=CC4=N2)C(=O)O | ||
| 分子式 | C19H12ClN3O2 | 分子量 | 349.77 |
| 溶解度 | ≥ 8.74mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.859 mL | 14.2951 mL | 28.5902 mL |
| 5 mM | 0.5718 mL | 2.859 mL | 5.718 mL |
| 10 mM | 0.2859 mL | 1.4295 mL | 2.859 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet