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5.09265

CX-5461

Name: CX-5461
Brand: MM

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

Synonym(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

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About This Item

Empirical Formula (Hill Notation):

C₂₇H₂₇N₇O₂S

CAS Number:

1138549-36-6

Molecular Weight:

513.61

MDL number:

MFCD21609261

UNSPSC Code:

12352200

NACRES:

NA.77

Assay:

≥97% (HPLC)

Form:

powder

Storage condition:

OK to freeze, protect from light

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Properties

Product Name

RNA Polymerase I Inhibitor II, CX-5461,

assay

≥97% (HPLC)

Quality Segment

100

form

powder

manufacturer/tradename

Calbiochem^®

storage condition

OK to freeze, protect from light

color

light beige

solubility

DMSO: 0.5 mg/mL, dilute acetic acid: 10 mg/mL

storage temp.

2-8°C

SMILES string

[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)

InChI key

XGPBJCHFROADCK-UHFFFAOYSA-N

Description

General description

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Pol I multi-protein complex

Reversible: yes

Packaging

Packaged under inert gas

Other Notes

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.

Legal Information

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

Disclaimer

Toxicity: Standard Handling (A)

Storage Class

11 - Combustible Solids

wgk

WGK 3

flash_point_f

Not applicable

flash_point_c