Description
CX-5461 is a potent small-molecule inhibitor of RNA polymerase (Pol) I.
Storage
2 years at -20 centigrade
Molecular Formula
C27H27N7O2S
Chemical Name
5H-Benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide, 2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-N-[(5-methyl-2-pyrazinyl)methyl]-5-oxo-
In vitro
CX-5461 is a potent small-molecule inhibitor of RNA polymerase (Pol) I. CX-5461 inhibit Pol I in the HCT-116 cells with IC50 of 142 nM. CX-5461 also inhibit Pol I in melanoma A375 cell line and pancreatic carcinoma MIA PaCa-2 cell line with IC50 of 113 nM and 54 nM.CX-5461 directly targets the Pol I machinery and inhibits Pol I transcription at the initiation stage.CX-5461 inhibits Pol I via disruption of the SL1-rDNA complex. And CX-5461 inhibits Pol I transcription without having an effect on DNA replication, protein translation, and general cellular transcription. As RNA polymerase (Pol) I is a multiprotein complex activated widely in cancer cells, CX-5461 can block cancer cell proliferation. CX-5461 inhibits the initiation stage of rRNA synthesis and induces both senescence and autophagy, but not apoptosis, through a p53-independent process in solid tumor cell lines. For example,CX-5461 induces autophagy but not apoptosis in A375 and MIA Paca-2 cancer cells.
In vivo
In two murine xenograft models of human cancers, pancreatic carcinoma (MIA PaCa-2) and melanoma (A375), CX-5461(50 mg/kg) demonstrated significant MIA PaCa-2 TGI with TGI equal to 69% on day 31.By inhibiting Pol I transcription, CX-5461 produce in vivo antitumor responses against solid tumors.
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