5.09265

CX-5461

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

• Sinonimo/i: 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
• Formula empirica (notazione di Hill): C₂₇H₂₇N₇O₂S
• Numero CAS: 1138549-36-6
• Peso molecolare: 513.61
• Numero MDL: MFCD21609261
• Codice UNSPSC: 12352200
• NACRES: NA.77

Proprietà

• Nome del prodotto: RNA Polymerase I Inhibitor II, CX-5461,
• Saggio: ≥97% (HPLC)
• Livello qualitativo: 100
• Stato: powder
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: light beige
• Solubilità: DMSO: 0.5 mg/mL; dilute acetic acid: 10 mg/mL
• Temperatura di conservazione: 2-8°C
• Stringa SMILE: [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); XGPBJCHFROADCK-UHFFFAOYSA-N

Descrizione

Descrizione generale

A cell-permeable benzothiazole compound that selectively inhibits RNA polymerase I-mediated pre-rRNA transcription (IC₅₀ = 142 nM in HCT-116), but not Pol II-mediated c-myc transcription, by preventing TAF SL1 and rDNA association). Effectively inhibits Pol I-dependent proliferation among 39 cancer cell lines (IC₅₀<1 µM) in vitro and suppresses A375 (50 mg/kg/d p.o.) and MIA PaCa-2 (50 mg/kg/3d p.o.) tumor expansion in vivo.

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.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
Pol I multi-protein complex

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Altre note

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.

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable