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Biological Activity:?

CX-5461 is the first potent, selective, and orally bioavailable inhibitor of RNA Polymerase I with an IC₅₀?~0.11 μM. ?It showed good in vivo activities in tumor models. It selectively blocks RNA PolI transcription, PIC assembly and SL1-rDNA interaction. CX-5461 showed potent anti-proliferation activity in cancer cells and antitumor activity in A375 and MiaPaca xenografts. In a recent Cancer Cell paper, CX5461 was shown to induce p53-dependent apoptotic cell death of Em-Myc lymphoma cells via activation of the Rp-MDM2-p53 nucleolar surveillance pathway; selectively induced p53-mediated cell death of lymphoma cells in vivo while sparing normal B cells.?

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How to Use:

• In vitro:? CX-5461 was used at 100-500 nM in vitro and in cell culture.
• In vivo:?In pancreatic carcinoma (MIA PaCa-2) and melanoma (A375) xenograft model, CX-5461 was administered orally at 50 mg/kg either once daily or every 3 days. In MV4;11 xenograft model, CX-5461 was administered intraperitoneally once a week at 125 mg/kg for the length of 25 days, or IP dosed at 25 mg/kg once a day on a 5-on, 2-off schedule over a period of 21 days.?

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