CX-5461, RNA Polymerase I inhibitor


Catalog No. size PriceQuantity
M66052-2D 1 mM in DMSO (1.95 mL) $79
M66052-2S 2 mg solid $149
M66052-10S 10 mg solid $589

Description

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.

  

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.

Products are for research use only. Not for human use.

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