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CAS No.: 1138549-36-6

CX-5461 Catalog No. CSN17133

Synonyms: Pidnarulex

CX-5461 is an inhibitor of rRNA synthesis, selectively inhibits Pol I-driven transcription of rRNA with IC50 of 142 nM.

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 Pol I-driven rRNA transcription

IC50:142nM
描述Deregulated ribosomal RNA synthesis is associated with uncontrolled cancer cell proliferation. RNA polymerase (Pol) I, the multiprotein complex that synthesizes rRNA, is activated widely in cancer. CX-5461, a potent small-molecule inhibitor of rRNA synthesis in cancer cells, selectively inhibits Pol I with IC₅₀ value of 142 nM in the HCT-116 cells. The IC₅₀ for rRNA synthesis for the BJ-hTert normal cell line of 74 nM correlated well with the IC₅₀ values of the solid tumor cell lines (IC₅₀ = 142, 113, and 54 nM, respectively) illustrating that CX-5461 can equivalently inhibit Pol I transcription in cancer and normal cells, but the normal cells can tolerate reductions in rRNA synthesis without induction of cell death. Treatment with 300 nM CX-5461 for 24 hours caused a significant increase from 15% ± 3% to 67% ± 2% in LC3B-II staining (P = 0.0041) in A375 and from 19% ± 2% to 62% ± 3% in LC3B-II staining (P = 0.002) in MIA PaCa-2 cells (LC3B-II, a known marker of autophagy). In addition to autophagy, CX-5461 (300 nM; 24 hours) was able to induce senescence in both cell lines. In two murine xenograft models of human cancers, MIA PaCa-2 and A375, CX-5461 was administered orally (50 mg/kg) either once daily or every 3 days. CX-5461 demonstrated significant MIA PaCa-2 TGI (tumor growth inhibition) equal to 69% on day 31. Likewise, CX-5461 demonstrated significant A375 TGI equal to 79% on day 32^[5].

动物研究

剂量

Mice: 30 mg/kg^[4] (i.v.)， 125 mg/kg^[1] (i.p.), 50 mg/kg^[1] (p.o.)

给药途径

i.v., i.p., p.o.

动物药代数据

Animal	Mice^[3]	Rats^[3]	Dogs^[3]	Monkeys^[3]
Dose	25 mg/kg	25 mg/kg	25 mg/kg	25 mg/kg
Administration	i.v. p.o.	i.v. p.o.	i.v. p.o.	i.v. p.o.
F	24% (p.o.)	29% (p.o.)	38% (p.o.)	45% (p.o.)
V_d	0.24 L/kg (i.v.)	0.08 L/kg (i.v.)	21 L/kg (i.v.)	33 L/kg (i.v.)
T_1/2	6.3 h (i.v.)	5.9 h (i.v.)	8.9 h (i.v.)	12.8 h (i.v.)
CL_s	0.03 L/h/kg (i.v.)	0.06 L/h/kg (i.v.)	1.6 L/h/kg (i.v.)	1.8 L/h/kg (i.v.)
AUC_0→24h	93373 ng·h/ml (p.o.)	92057 ng·h/ml (p.o.)	3890 ng·h/mL (p.o.)	2597 ng·h/mL (p.o.)

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
NCT02719977	Cancer	Phase 1	Recruiting	April 2019	Canada, British Columbia ... more >> BCCA - Vancouver Cancer Centre Recruiting Vancouver, British Columbia, Canada, V5Z 4E6 Contact: Karen Gelmon 604 877-6000 ext 2032 Canada, Ontario Ottawa Hospital Research Institute Recruiting Ottawa, Ontario, Canada, K1H 8L6 Contact: John Hilton 613 737-7700 ext 70179 University Health Network Recruiting Toronto, Ontario, Canada, M5G 2M9 Contact: David Cescon 416 946-2245 Collapse <<

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.9470 mL
- 9.7349 mL
- 19.4699 mL
- 5 mM
- 0.3894 mL
- 1.9470 mL
- 3.8940 mL
- 10 mM
- 0.1947 mL
- 0.9735 mL
- 1.9470 mL

技术信息

CAS号

1138549-36-6

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C27H27N7O2S

运输

蓝冰

分子量

513.61

别名

Pidnarulex

溶解度

DMSO	Insoluble
Water	Insoluble

动物实验配方

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