CX-5461

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WARNING: This product is for research use only, not for human or veterinary use.

Description:CX-5461 is a first-in-class non-genotoxic small molecule targeted inhibitor of RNA polymerase I (Pol I) that activates the p53 pathway without causing DNA damage. CX-5461 selectively inhibits rRNA synthesis by Pol I in the nucleolus, but does not inhibit mRNA synthesis by RNA Polymerase II (Pol II) and does not inhibit DNA replication or protein synthesis. Inhibition of Pol I results in nucleolar stress and release of ribosomal proteins (RP) from the nucleolus. The RP bind to Mdm2 and liberate p53 to orchestrate apoptosis in cancer cells. CX-5461 demonstrates a favorable preclinical profile, potently and selectively kills cancer cells, demonstrates robust in vivo efficacy in multiple models, and has demonstrated oral bioavailability in multiple species.

Price and Availability

CX-5461, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200848Name: CX-5461CAS#: 1138549-36-6Chemical Formula: C27H27N7O2SExact Mass: 513.19469Molecular Weight: 513.61Elemental Analysis:C, 63.14; H, 5.30; N, 19.09; O, 6.23; S, 6.24

Synonym:CX5461; CX 5461; CX-5461; Pidnarulex

IUPAC/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

InChi Key:XGPBJCHFROADCK-UHFFFAOYSA-N

InChi Code: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)

SMILES Code:O=C(C1=C(SC2=CC=CC=C23)N3C4=C(C=CC(N5CCN(C)CCC5)=N4)C1=O)NCC6=NC=C(C)N=C6

Technical Data

Additional Information

References

1: Quin JE, Devlin JR, Cameron D, Hannan KM, PearsonRB, Hannan RD. Targeting the nucleolus for cancer intervention. BiochimBiophys Acta. 2014 Jun;1842(6):802-816. doi:10.1016/j.bbadis.2013.12.009. Epub 2014 Jan 2. Review. PubMed PMID:24389329.

2: Achiron A, Mashiach R, Zilkha-Falb R, Meijler MM, Gurevich M.Polymerase I pathway inhibitor ameliorates experimental autoimmuneencephalomyelitis. J Neuroimmunol. 2013 Oct 15;263(1-2):91-7. doi:10.1016/j.jneuroim.2013.08.002. Epub 2013 Aug 15. PubMed PMID: 23998422.

3: Bywater MJ, Poortinga G, Sanij E, Hein N, Peck A, Cullinane C, WallM, Cluse L, Drygin D, Anderes K, Huser N, Proffitt C, Bliesath J,Haddach M, Schwaebe MK, Ryckman DM, Rice WG, Schmitt C, Lowe SW,Johnstone RW, Pearson RB, McArthur GA, Hannan RD. Inhibition of RNApolymerase I as a therapeutic strategy to promote cancer-specificactivation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65. doi:10.1016/j.ccr.2012.05.019. PubMed PMID: 22789538; PubMed Central PMCID:PMC3749732.

4: Drygin D, Lin A, Bliesath J, Ho CB, O"Brien SE, Proffitt C, Omori M,Haddach M, Schwaebe MK, Siddiqui-Jain A, Streiner N, Quin JE, Sanij E,Bywater MJ, Hannan RD, Ryckman D, Anderes K, Rice WG. Targeting RNApolymerase I with an oral small molecule CX-5461 inhibits ribosomal RNAsynthesis and solid tumor growth. Cancer Res. 2011 Feb 15;71(4):1418-30.doi: 10.1158/0008-5472.CAN-10-1728. Epub 2010 Dec 15. PubMed PMID:21159662.