CX-5461 is an inhibitor of ribosomal RNA (rRNA) synthesis. It selectively inhibits RNA polymerase I-driven transcription of rRNA in HCT116, A375, and MIA PaCa-2 tumor cells (IC50s = 142, 113, and 54 nM, respectively) without affecting RNA polymerase II (IC50 > 25?M), DNA replication, or protein translation.1,2 At 50 mg/kg, CX-5461 demonstrates in vivo antitumor activity against human solid tumors in mouse xenograft models.1
1.Drygin, D., Lin, A., Bliesath, J., et al.Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growthCancer Res.71(4)1418-1430(2011) 2.Haddach, M., Schwaebe, M.K., Michaux, J., et al.Discovery of CX-5461, the first direct and selective inhibitor of RNA polymerase I, for cancer therapeuticsACS Med. Chem. Lett.3(7)602-606(2012)