CX-4945 (Silmitasertib)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
CX-4945(Silmitasertib)是一种有效的、选择性的、可口服的和ATP竞争性的酪蛋白激酶2(CK2)抑制剂,IC50值为1 nM[1]。
据报道,CX-4945在一系列肿瘤细胞系中均具有抗增殖活性。CX-4945通过抑制Akt Ser129的磷酸化,而非激活PTEN,从而抑制CK2调节的PI3K / Akt信号通路。此外,CX-4945处理的细胞可以减少p21磷酸化、上调p21和p27的总量。在BT-474乳腺癌细胞系中,CX-4945诱导细胞周期停滞在G2/M期。而在BxPC-3胰腺癌细胞系中,CX-4945也可以诱导细胞周期停滞在G1期[1]。
在CX-4945和BxPC-3衍生的小鼠异种移植模型中,CX-4945减少磷酸化p21的表达,并具有抗癌活性[1]。
参考文献:
[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.
- 1. Swati Mishra, Chizuru Kinoshita, et al. "Evaluation of a Selective Chemical Probe Validates That CK2 Mediates Neuroinflammation in a Human Induced Pluripotent Stem Cell-Derived Mircroglial Model." Front Mol Neurosci. 2022 Jun 14;15:824956. PMID: 35774866
- 2. Silva-Pavez E, Villar P, et al. "CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells." Cell Death Dis.2019 Jan 25;10(2):73. PMID: 30683840
- 3. Zhao Z, Wang L, et al."Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia." Genes Dev. 2019 Jan 1;33(1-2):61-74. PMID: 30573454
- 4. Tanghe G, Urwyler-Rösselet C, et al. "RIPK4 activity in keratinocytes is controlled by the SCF(β-TrCP) ubiquitin ligase to maintain cortical actin organization." Cell Mol Life Sci. 2018 Feb 12. PMID: 29435596
- 5. Wu F, Qiu J, et al. "Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gα(i)/Gα(q)-CK2 signaling in ischemic stroke." Exp Neurol. 2018 Apr;302:136-144. PMID: 29337146
- 6. Krentz Gober, Madeline J. "GENE EXPRESSION PROFILES REVEAL ALTERNATIVE TARGETS OF THERAPEUTICINTERVENTION FOR THE TREATMENT OF DRUG-RESISTANT NON-SMALL CELL LUNG CANCERS" (2017).Thesesand Dissertations--Pharmacy. 78.
- 7. Korb E, Herre M, et al. "Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition." Cell. 2017 Aug 12. PMID: 28823556
- 8. Viscarra JA, Wang Y, et al. "Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2." Sci Signal. 2017 Feb 21;10(467). pii: eaai8596. PMID: 28223413
- 9. Kubiński K, Masłyk M, Orzeszko A. "Benzimidazole inhibitors of protein kinase CK2 potently inhibit the activity of atypical protein kinase Rio1." Mol Cell Biochem. 2017 Feb;426(1-2):195-203. PMID: 27909846
- 10. Dubois N, Willems M, et al. "Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential." Int J Oncol. 2016 Jun;48(6):2445-52. PMID: 27098015
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 349.77 |
Cas No. | 1009820-21-6 |
Formula | C19H12ClN3O2 |
Synonyms | CX 4945;CX4945 |
Solubility | ≥103.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid |
SDF | Download SDF |
Canonical SMILES | C1=CC(=CC(=C1)Cl)NC2=C3C=CN=CC3=C4C=CC(=CC4=N2)C(=O)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
Jurkat细胞 |
溶解方法 |
在DMSO中的溶解度 >10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
4天;IC50 值为 0.1 μM |
应用 |
通过测定CK2对Akt特异性磷酸化位点(S129)的磷酸化水平来确定CK2的抑制。CX-4945诱导Akt(S129)的去磷酸化,并诱导Akt底物p21(T145)的快速去磷酸化。CX-4945诱导细胞凋亡。在Jurkat细胞中,CX-4945也有效抑制内源性CK2的活性,IC50值为0.1μM。 |
动物实验[1]: | |
动物模型 |
无胸腺小鼠 |
剂量 |
75 mg/kg;2次/日(bid);口服给药 |
应用 |
在人前列腺癌PC3异种移植无胸腺小鼠模型中评估CX-4945的体内效应。皮下植入PC3肿瘤的小鼠用CX-4945(25 mg/kg、50 mg/kg和75 mg/kg,p.o,bid)处理,与对照组相比,CX-4945诱导肿瘤生长抑制(TGI分别为19%、40%和86%),具有剂量反应性的效应。CX-4945在小鼠中耐受性良好,与对照组相比,在治疗期间具有最小的体重变化。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
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. |
描述 | CX-4945 (Silmitasertib)是一种有效的和选择性的酪蛋白激酶2(CK2)抑制剂,IC50值为1 nM。 | |||||
靶点 | CK2α | CK2α' | ||||
IC50 | 1 nM | 1 nM |
质量控制和MSDS
- 批次: