| 产品介绍 |
CX-5461是rRNA合成抑制剂，选择性抑制Pol I驱动的rRNA转录，IC50为142nM，对Pol II无效。 |
| 备注 |
CX-5461 is an inhibitor of rRNA synthesis, selectively inhibits Pol I-driven transcription of rRNA with IC50 of 142 nM, has no effect on Pol II, and possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA repli |
| 生化机理 |
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. cGMP manufacture has been completed and the molecule is being advanced to the clinic and will be developed for the treatment of leukemias, lymphomas and multiple myeloma. (source: Cylene Pharmaceuticals website) |
| 别名 |
CX 5461;CX5461;2-(4-甲基-1H-1,4-二氮杂环庚烷-1-基)-N-((5-甲基-2-吡嗪基)甲基)-5-氧代-5H-苯并噻唑并(3,2-a)(1,8)萘啶-6-甲酰胺;;CX 5461;CX5461;2-(hexahydro-4-methyl-1h-1,4-diazepin-1-yl)-n-((5-methyl-2-pyrazinyl)methyl)-5-oxo-5h-benzothiazolo(3,2-a)(1,8)naphthyridine-6-carboxamide |
