英文名稱 | CX-5461 | Pidnarulex |
---|---|
中文名稱 | CX-5461 |
CAS號 | 1138549-36-6 |
分子式 | C27H27N7O2S |
分子量 | 513.61 |
外觀 | White to yellow powder |
儲存條件 | Dry, dark and at 0 - 4 ℃ for short term (days to weeks) or -20 ℃ for long term (months to years). |
英文名稱 | CX-5461 | Pidnarulex |
---|---|
中文名稱 | CX-5461 |
CAS號 | 1138549-36-6 |
分子式 | C27H27N7O2S |
分子量 | 513.61 |
外觀 | White to yellow powder |
儲存條件 | Dry, dark and at 0 - 4 ℃ for short term (days to weeks) or -20 ℃ for long term (months to years). |
CX-5461 is a first-in-class non-genotoxic small molecule targeted inhibitor of RNA polymerase I (Pol I) that activates the p53 pathway without causing DNA damage. CX-5461 selectively inhibits rRNA synthesis by Pol I in the nucleolus, but does not inhibit mRNA synthesis by RNA Polymerase II (Pol II) and does not inhibit DNA replication or protein synthesis. Inhibition of Pol I results in nucleolar stress and release of ribosomal proteins (RP) from the nucleolus. The RP bind to Mdm2 and liberate p53 to orchestrate apoptosis in cancer cells. CX-5461 demonstrates a favorable preclinical profile, potently and selectively kills cancer cells, demonstrates robust in vivo efficacy in multiple models, and has demonstrated oral bioavailability in multiple species.
PMID: 21159662 DOI: 10.1158/0008-5472.CAN-10-1728
PMID: 22789538 PMCID: PMC3749732 DOI: 10.1016/j.ccr.2012.05.019