CX-5461

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.

Cell permeable: yes

Primary Target
Pol I multi-protein complex

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

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.

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