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| | CX-5461 Basic information |
| Product Name: | CX-5461 | | Synonyms: | CX-5461;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;RNA Polymerase I Inhibitor II, CX-5461 - CAS 1138549-36-6 - Calbiochem;CS-1938;2-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-N-[(5-methyl-2-pyrazinyl)methyl]-5-oxo-5H-benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide;CX-5461/CX5461;2-(Hexahydro-4-Methyl-1H-1,4-diazepin-1-yl)-N-[(5-Methyl-2-pyrazinyl)Methyl]-5-oxo-5H-benzothiazolo[3,2-a][1,8]napht;5H-Benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide, 2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-N-[(5-methyl-2-pyrazinyl)methyl]-5-oxo- | | CAS: | 1138549-36-6 | | MF: | C27H27N7O2S | | MW: | 513.61 | | EINECS: | | | Product Categories: | apis;Inhibitors | | Mol File: | 1138549-36-6.mol |  |
| | CX-5461 Chemical Properties |
| Boiling point | 739.9±60.0 °C(Predicted) | | density | 1.45 | | storage temp. | +2C to +8C | | solubility | insoluble in H2O; insoluble in EtOH; insoluble in DMSO | | form | Light beige powder | | pka | 8.53±0.20(Predicted) |
| | CX-5461 Usage And Synthesis |
| Definition | ChEBI: CX-5461 is an organic heterotetracyclic compound that is 5-oxo-5H-[1,3]benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxylic acid substituted by a 4-methyl-1,4-diazepan-1-yl group at position 2 and in which the carboxy group at position 6 is substituted by a [(5-methylpyrazin-2-yl)methyl]nitrilo group. An inhibitor of ribosomal RNA (rRNA) synthesis which specifically inhibits RNA polymerase I-driven transcription of rRNA in several cancer cell lines. It is currently in phase I/II clinical trials for advanced hematologic malignancies and triple-negative breast cancer with BRCA1/2 mutation. It has a role as an antineoplastic agent, an apoptosis inducer and an EC 2.7.7.6 (RNA polymerase) inhibitor. It is a diazepine, an organic heterotetracyclic compound, a member of pyrazines, a secondary carboxamide and a naphthyridine derivative. | | General Description | 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. | | Biological Activity | cx-5461 is a potent and orally bioavailable small-molecule inhibitor of rrna synthesis that specifically inhibits rna polymerase (pol) i-driven transcription with ic50 value of 142 nm. cx-5461 exhibits antiproliferative activity against human pancreatic tumor cells mia paca-2, human melanoma cells a375 and colorectal carcinoma cells hct-116 with ec50 values of 74, 58, and 167 nmol/l, respectively. [1].cx-5461 was revealed to inhibit pol i transcription via promoting the stabilization of p53. in addition, cx-5461 has been demonstrated to induce autophagy and senescence but not apoptosis in mia paca-2 and a375 cell lines. | | Biochem/physiol Actions | Cell permeable: yes | | in vivo | cx-5461 has shown to suppress tumor volume in both mia paca-2 and a375 derived xenograft mice models [1]. | | target | Pol I | | references | [1] drygin d1, 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 rna polymerase i with an oral small molecule cx-5461 inhibits ribosomal rna synthesis and solid tumor growth. cancer res. 2011 feb 15;71(4):1418-30 |
| | CX-5461 Preparation Products And Raw materials |
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