Inhibiteur de l'ARN polyméase I II; CX-5461

Non disponible en dehors du Royaume-Uni et de l'Irlande

Biochem/physiol Actions

Reversible: yes

Primary TargetPol I multi-protein complex

Cell permeable: yes

General description

A cell-permeable benzothiazole compound that selectively inhibits RNA polymerase I-mediated pre-rRNA transcription (IC₅₀ = 142 nM in HCT-116), but not Pol II-mediated c-myc transcription, by preventing TAF SL1 and rDNA association). Effectively inhibits Pol I-dependent proliferation among 39 cancer cell lines (IC₅₀﹤1 µM) in vitro and suppresses A375 (50 mg/kg/d p.o.) and MIA PaCa-2 (50 mg/kg/3d p.o.) tumor expansion in vivo.

A cell-permeable benzothiazole compound that selectively inhibits RNA polymerase I-mediated pre-rRNA transcription (IC₅₀ = 142, 113, 54, and 74 nM in HCT-116, A375, MIA PaCa-2, and BJ-hTert cells, respectively), but not Pol II-mediated c-myc transcription, by preventing TAF (TATA Binding Protein-/TBP-Associated Factor) SL1 and rDNA association, effectively inhibiting Pol I-dependent proliferation among 39 cancer cell lines (IC₅₀﹤1 µM) in vitro. While Pol I inhibition by CX-5461 is shown to result in p53-dependent apoptosis in cancer cells of hematopoietic origin, cell death by CX-5461 treatment in solid tumors-derived A375 and MIA PaCa-2 cultures are primarily due to autophagy and senescence, but not apoptosis, induction. Shown to suppress A375 (50 mg/kg/d p.o.) and MIA PaCa-2 (50 mg/kg/3d p.o.) tumor expansion, as well as selectively induce p53-mediated cell death of Eµ-Myc lymphoma, but not normal B cells, in mice (50 mg/kg p.o.) in vivo.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Haddach, M., et al. 2012. ACS Med. Chem. Lett.3, 602.Bywater, M.J., et al. 2012. Cancer Cell22, 51.Drygin, D., et al. 2011. Cancer Res71, 1418.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Warning

Toxicity: Standard Handling (A)