CX5461 是一种口服有效的rRNA合成抑制剂，可抑制 Pol I 驱动的 rRNA 转录。

CX-5461, a selective inhibitor of rRNA synthesis, suppresses Pol I-driven transcription of rRNA.

在异种移植人固体肿瘤的小鼠模型中,通过口服CX-5461(50 mg/kg)表现出抗实体瘤活性.

在HCT-116（EC50=167 nM）,A375（EC50=58 nM）,和MIA PaCa-2（和EC50=74 nM）细胞系中,CX-5461能够抑制细胞增殖。在固体肿瘤细胞中,CX-5461诱导细胞自噬或衰老,但不诱导细胞凋亡,其中qi黑色素瘤 A375 (Pol I IC50 = 113 nM；Pol II IC50 >25 μM)和胰腺癌MIA PaCa-2 (Pol I IC50=54 nM；Pol II IC50 ~25 mM)。在HCT-116细胞中,CX-5461选择性抑制rRNA合成,Pol I（IC50=142 nM）,Pol II （IC50 >25 μM）。

Pol I and Pol II Transcription Assay: Two short-lived RNA transcripts (half-lives ~20-30 minutes), one produced by Pol I and another by Pol II, are quantitated by qRT-PCR as a measure of CX-5461-related effects on transcription. The 45S pre-rRNA served as the Pol I transcript and the mRNA for the protooncogene c-myc served as the comparator Pol II transcript. Both Pol I and Pol II transcription are known to be affected by general cellular stress. To minimize the potential effects of such stress, cells are exposed to test agents for only a short period of time (2 hours). This is sufficient time for these transcripts to be reduced by greater than 90% if CX-5461 affects their synthesis.

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(Only for Reference)

1138549-36-6

C27H27N7O2S

513.62

DMSO:5.14 mg/ml (10 mM),Need ultrasonic
H2O:Insoluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years