CX5461 as intravenous infusion on day 1 and day 8 every 4 weeks. A day 1 every 3 weeks schedule may be used if the day 1 and day 8 every 4 weeks schedule is not tolerable.

ChIP analysis was employed to investigate the effects of CX-5461 on the association of various components of the Pol I multiprotein complex with the rDNA promoter. Treatment of HCT-116 colorectal carcinoma cells, A375, or MIA PaCa-2 with 2 μmol/L CX-5461 resulted in 40% to 60% reduction of the Pol I enzyme association with the rDNA promoter. Further, CX-5461 significantly depleted the binding of Pol I transcription factors (TF) to the rDNA promoter in HCT-116 cells, with the TBP (is a member of both Pol I and Pol II transcription machineries) and TAFI110 subunits of SL1 (TBP, TAFI110, TAFI63) being most overtly affected. To ensure that CX-5461 selectively inhibits rRNA transcription but not DNA or protein synthesis, HCT-116, A375, and MIA PaCa-2 cells were preincubated with 10 μmol/L CX-5461 for 60 minutes. In dose–response studies, the IC50 for inhibition of DNA synthesis in A375 and MIA PaCa-2 cell lines ranged from 16.8 to 27.9 μmol/L, whereas a high-test dose of 30 μmol/L CX-5461 had no significant effect on proteins synthesis. Thus, CX-5461 possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA replication and protein translation.