产品详情
简单介绍：
CX-5461,RNAPolymeraseIinhibitor
详情介绍：
Product Information
| Molecular Weight: | 513.61 |
| Formula: | C27H27N7O2S |
| Purity: | ≥98% |
| CAS#: | 1138549-36-6 |
| Solubility: | DMSO up to 2 mM |
| Chemical Name: | 2-(4-methyl-1,4-diazepan-1-yl)-N-((5-methylpyrazin-2-yl)methyl)-5-oxo-5H-benzo[4,5]thiazolo[3,2-a][1,8]naphthyridine-6-carboxamide |
| Storage: | Powder: 4oC 1 year. DMSO: 4oC 3 month; -20oC 1 year. |
Details
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.
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.
Reference:
- 1. Drygin D, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. (2011) Cancer Res. 71(4):1418-30.
- 2. Haddach M, et al. Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase I, for Cancer Therapeutics. (2012) ACS Med. Chem. Lett., 3 (7), pp 602–606.
- 3. Bywater MJ, et al Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. (2012) Cancer Cell, 22(1), 51 – 65.
- Product Specification:
- Product MSDS:
Products are for research use only. Not for human use.
相关文章
