5.09265

CX-5461

≥97% (HPLC), powder, RNA polymerase inhibitor, Calbiochem^®

• Sinônimo(s): RNA Polymerase I Inhibitor II, CX-5461, Pol I Inhibitor II, CX5461, 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
• Fórmula empírica (Notação de Hill): C₂₇H₂₇N₇O₂S
• Número CAS: 1138549-36-6
• Peso molecular: 513.61
• Número MDL: MFCD21609261
• Código UNSPSC: 12352200
• NACRES: NA.77

Propriedades

• Nome do produto: RNA Polymerase I Inhibitor II, CX-5461,
• Ensaio: ≥97% (HPLC)
• Nível de qualidade: 100
• Formulário: powder
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: light beige
• solubilidade: DMSO: 0.5 mg/mL; dilute acetic acid: 10 mg/mL
• temperatura de armazenamento: 2-8°C
• cadeia de caracteres SMILES: [s]1c2[n](c4nc(ccc4[c](c2C(=O)NCc6ncc(nc6)C)=O)N5CCN(CCC5)C)c3c1cccc3
• InChI: 1S/C27H27N7O2S/c1-17-14-29-18(15-28-17)16-30-26(36)23-24(35)19-8-9-22(33-11-5-10-32(2)12-13-33)31-25(19)34-20-6-3-4-7-21(20)37-27(23)34/h3-4,6-9,14-15H,5,10-13,16H2,1-2H3,(H,30,36)
• chave InChI: XGPBJCHFROADCK-UHFFFAOYSA-N

Descrição

Descrição geral

A cell-permeable benzothiazole compound that selectively inhibits RNA polymerase I-mediated pre-rRNA transcription (IC₅₀ = 142, 113, 54, and 74 nM in HCT-116, A375, MIA PaCa-2, and BJ-hTert cells, respectively), but not Pol II-mediated c-myc transcription, by preventing TAF (TATA Binding Protein-/TBP-Associated Factor) SL1 and rDNA association, effectively inhibiting Pol I-dependent proliferation among 39 cancer cell lines (IC₅₀<1 µM) in vitro. While Pol I inhibition by CX-5461 is shown to result in p53-dependent apoptosis in cancer cells of hematopoietic origin, cell death by CX-5461 treatment in solid tumors-derived A375 and MIA PaCa-2 cultures are primarily due to autophagy and senescence, but not apoptosis, induction. Shown to suppress A375 (50 mg/kg/d p.o.) and MIA PaCa-2 (50 mg/kg/3d p.o.) tumor expansion, as well as selectively induce p53-mediated cell death of Eμ-Myc lymphoma, but not normal B cells, in mice (50 mg/kg p.o.) in vivo.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
Pol I multi-protein complex

Reversible: yes

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Outras notas

Haddach, M., et al. 2012. ACS Med. Chem. Lett.3, 602.
Bywater, M.J., et al. 2012. Cancer Cell22, 51.
Drygin, D., et al. 2011. Cancer Res71, 1418.

Informações legais

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable