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Silmitasertib

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Chemical Structure| 1009820-21-6 同义名 : CX-4945
CAS号 : 1009820-21-6
货号 : A103748
分子式 : C19H12ClN3O2
纯度 : 99%+
分子量 : 349.771
MDL号 : MFCD13184796
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(100.07 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

0.1 M NaOH: 30 mg/mL(85.77 mM)，配合低频超声，并调节pH至9
动物实验配方：

1% CMC Na+water 30 mg/mL suspension

生物活性
靶点

  • CK2

    CK2, IC50:1 nM
描述 Silmitasertib (CX-4945) leads to cell-cycle arrest and selectively induces apoptosis in cancer cells compared to normal cells. This action is associated with the attenuation of PI3K/Akt signaling and the antiproliferative activity of Silmitasertib is linked to the expression levels of the CK2α catalytic subunit[1]. When combined with PS-341, Silmitasertib prevents leukemic cells from initiating a functional unfolded protein response (UPR) to counteract PS-341-induced proteotoxic stress in the ER lumen. It also reduces the expression of the pro-survival ER chaperone BIP/Grp78[2]. Silmitasertib induces cytotoxicity and apoptosis and exerts antiproliferative effects in hematological tumors. It achieves these effects by downregulating CK2 expression and inhibiting the activation of CK2-mediated PI3K/Akt/mTOR signaling pathways[3].
作用机制 CX-4945 acts as an ATP-competitive inhibitor of both isoforms of CK2 catalytic subunits, CK2α and CK2α’, directly blocking the phosphorylation of Akt at Serine 129 in PI3K/Akt signaling pathway.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A431 10 μM Function Assay 30 min attenuates PI3K-Akt-mTOR signaling 22387988
A431 10 μM Function Assay 4-24 h enhances apoptosis with erlotinib 22387988
A549 3/10 μM Function Assay 48 h suppresses the micropillar-induced expression of p-FAK 26318800
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00891280 Advanced Solid Tumors ... 展开 >> Breast Cancer Inflammatory Breast Cancer Castleman's Disease Multiple Myeloma 收起 << Phase 1 Unknown December 2011 United States, Arizona ... 展开 >> Mayo Clinic Arizona Recruiting Scottsdale, Arizona, United States, 85259 Contact: Clinical Trials Office Mayo Clinic Cancer Center    507-538-7623       Principal Investigator: Donald Northfelt, MD          United States, Colorado Front Range Cancer Specialists Recruiting Fort Collins, Colorado, United States, 80528 Contact: P. Zeller    970-212-7609       Principal Investigator: Robert F Marschke, MD          Front Range Cancer Specialists Recruiting Loveland, Colorado, United States, 80528 Contact: Pat Zeller    970-212-7609       Principal Investigator: R. McFarland, MD          United States, Texas U T M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: R. Alvarez, MD       ralvarez@mdanderson.org    Principal Investigator: R. Alvarez, MD 收起 <<
NCT03571438 Kidney Cancer Not Applicable Recruiting September 30, 2024 France ... 展开 >> Grenoble Alps Hospital Recruiting Grenoble, France, 38043 Contact: Jean-Luc Descotes, PU-PH 收起 <<
NCT02128282 Cholangiocarcinoma Phase 1 Phase 2 Recruiting November 2021 United States, Arizona ... 展开 >> Mayo Clinic Recruiting Scottsdale, Arizona, United States, 85259-5499 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Mitesh Borad, M.D.          United States, Colorado University of Colorado- Denver Recruiting Aurora, Colorado, United States, 80045 Contact: Amy Szilard    720-848-0702    Amy.Szilard@ucdenver.edu    Principal Investigator: Sarah (Lindsey) Davis, MD          United States, Florida Mayo Clinic Recruiting Jacksonville, Florida, United States, 32224 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Kabir Mody, MD          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Joleen Hubbard, MD          United States, Texas Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting Dallas, Texas, United States, 75246 Contact: Tammy Carmical, RN    214-370-1937    tammy.carmical@usoncology.com    Principal Investigator: Carlos Becerra, M.D.          Texas Oncology-Tyler Recruiting Tyler, Texas, United States, 75702 Contact: Karen Poe, RN    903-579-9869    karen.poe@usoncology.com    Principal Investigator: Donald A Richards, M.D.          Korea, Republic of Asan Medical Center Recruiting Seoul, Songpa-gu, Korea, Republic of, 138-736 Contact: Heung-Moon Chang, MD    82-3010-3219 ext 3210    changhm@amc.seoul.kr    Contact: Seok kyung Jeong    82-2-3010-5634    jsk0213@amc.seoul.kr    Samsung Medical Center Recruiting Seoul, Korea, Republic of Contact: Eunyou Lee    82-2-3410-0955    ley0709@samsung.com    Principal Investigator: Joon Oh Park, MD          Seoul National University Hospital Recruiting Seoul, Korea, Republic of Contact: Myoungsun Choi    82-2-2072-7612    iamyou3@hanmail.net    Principal Investigator: Do-Youn Oh, MD          Severance Hospital, Yonsei University Health System Recruiting Seoul, Korea, Republic of Contact: So Young Hwang    82-2-2228-8180    syhwang@yuhs.ac    Principal Investigator: Sun Young Rha, MD          Taiwan China Medical University Hospital Recruiting Taichung City, Taiwan Contact: Pei-Chen Hsu    +886-4-2205-2121    peggyshiu0807@gmail.com    Principal Investigator: Li-Yuan Bai, M.D. 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.86mL

0.57mL

0.29mL

14.30mL

2.86mL

1.43mL

28.59mL

5.72mL

2.86mL
参考文献

[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 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.

[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.