CX-5461

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

CX-5461  纯度: 98.18%

CX-5461 是一种有效,口服的 rRNA 合成抑制剂。在 HCT-116,A375 和 MIA PaCa-2 细胞中抑制 RNA 聚合酶 I 驱动的 rRNA 转录,IC50 为 142,113 和 54 nM。

CX-5461

CX-5461 Chemical Structure

CAS No. : 1138549-36-6

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
5 mg ¥1100 In-stock
10 mg ¥1800 In-stock
50 mg ¥5400 In-stock
100 mg   询价  
200 mg   询价  

* Please select Quantity before adding items.

CX-5461 相关产品

相关化合物库:

  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Cell Cycle/DNA Damage Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Anti-Aging Compound Library
  • Orally Active Compound Library
  • Anti-Blood Cancer Compound Library

生物活性

CX-5461 is a potent and oral rRNA synthesis inhibitor. It inhibits RNA polymerase I-driven transcription of rRNA with IC50s of 142, 113, and 54 nM in HCT-116, A375, and MIA PaCa-2 cells, respectively[1].

IC50 & Target

IC50: 54 nM (rRNA synthesis, MIA PaCa-2 cells), 113 nM (rRNA synthesis, A375 cells), 142 nM (rRNA synthesis, HCT-116 cells)[1]

体外研究
(In Vitro)

CX-5461 is a potent and orally bioavailable inhibitor of Pol I-mediated rRNA synthesis, with IC50s of 142 nM in HCT-116, 113 nM in A375, and 54 nM in MIA PaCa-2 cells, and shows little or no effect on Pol II (IC50, ≥25 μM). CX-5461 has modest inhibition on DNA replication and protein translation. CX-5461 also exhibits broad antiproliferative activity against a panel of human cancer cell lines, with a mean EC50 of 147 nM, but has minimal effect on viability of nontransformed human cells, with EC50 values of appr 5000 nM. EC50s of CX-5461 for HCT-116, A375, and MIA PaCa-2 cell lines are 167, 58, and 74 nM, respectively. CX-5461 induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process[1]. Eμ-Myc lymphoma cells from tumor-bearing mice are exquisitely sensitive to CX-5461 with an IC50 of 27.3 nM ± 8.1 nM for Pol I transcription after 1 hr and IC50 of 5.4 nM ± 2.1 nM for cell death after 16 hr. CX-5461 activates p53 via the nucleolar stress response in Eμ-MycLymphoma Cells[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

CX-5461 displays antitumor activity against human solid tumors in murine xenograft models. CX-5461 (50 mg/kg, p.o.) shows significant MIA PaCa-2 growth inhibition with TGI equal to 69% on day 31 and 79% TGI on A375 on day 32[1]. CX-5461 (50 mg/kg, p.o.) inhibits the Eμ-Myc tumor cells with 84% repression in Pol I transcription at 1 hr posttreatment in C57BL/6 mice. CX-5461 also induces a rapid reduction in tumor burden in the lymph nodes and a concomitant reduction of spleen size to within the normal range[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

513.61

Formula

C27H27N7O2S

CAS 号

1138549-36-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 2 mg/mL (3.89 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.9470 mL 9.7350 mL 19.4700 mL
5 mM
10 mM

*

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, 6 months; -20°C, 1 month。-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。

参考文献
  • [1]. Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011 Feb 15;71(4):1418-30.

    [2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65.

Cell Assay
[1]

Cells are plated on 96-well plates and treated the next day with dose response of CX-5461 for 96 hours. Cell viability is determined using Alamar Blue and CyQUANT assays[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice[1]
Animal experiments are performed with 5- to 6-week-old female athymic (NCr nu/nu fisol) mice of Balb/c. Mice are inoculated with athymic (NCr nu/nu fisol) mice in 100 μL of cell suspension subcutaneously in the right flank. Tumor measurements are performed by caliper analysis, and tumor volume is calculated using the formula (l×w2)/2, where w=width and l=length in mm of the tumor. established tumors (appr 110-120 mm3) are randomized into vehicle (50 mM NaH2PO4, pH 4.5), NSC 613327, or CX-5461 treatment groups. Tumor growth inhibition (TGI) is determined on the last day of study according to the formula: TGI (%)=[100 − (VfD− ViD)/ (VfV − ViV) × 100], where ViV is the initial mean tumor volume in vehicle-treated group, VfV is the final mean tumor volume in vehicle-treated group, ViD is the initial mean tumor volume in drug-treated group, and VfD is the final mean tumor volume in drug-treated group.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011 Feb 15;71(4):1418-30.

    [2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务