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CX-5461 (Synonyms: CX 5461;CX5461)

Catalog No.GC14404

Pol I-mediated rRNA synthesis inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

CX-5461 Chemical Structure

Cas No.: 1138549-36-6

Size Price Stock Qty
5mg
$81.00
In stock
10mg
$115.00
In stock
50mg
$382.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell Experiments: [1]

Cell lines

hTERT-immortalized BJ-hTERT human fibroblasts, Human inflammatory breast cancer cell lines SUM 149PT and SUM 190PT, Human eosinophilic leukemia cell line EOL-1, human B cell precursor leukemia cell line SEM, and human acute monocytic leukemia cell line THP-1

Preparation method

Stored at room temperature as 10 mmol/L stock solutions in 50 mmol/L NaH2PO4?(pH 4.5)

Reacting condition

2 μmol/L, 1 hour

Applications

Treatment of HCT-116, A375, or MIA PaCa-2 with 2 μmol/L CX-5461 resulted in 40% to 60% reduction of the Pol I enzyme association with the rDNA promoter. CX-5461 significantly depleted the binding of Pol I transcription factors (TF) to the rDNA promoter in HCT-116 cells. In dose-response studies, the IC50?for inhibition of DNA synthesis in A375 and MIA PaCa-2 cell lines ranged from 16.8 to 27.9 μmol/L. Treatment of solid tumor cell lines with CX-5461 induced cellular senescence and autophagy through selective inhibition of rRNA synthesis. CX-5461 targets the SL1 transcription factor of the Pol I complex and induces autophagy and senescence among solid tumor cell lines and selectively kills cancer cells relative to normal cells.

Animal experiment: [1]

Animal models

Murine xenograft models of human cancers, pancreatic carcinoma (MIA PaCa-2) and melanoma (A375)

Dosage form

Administered orally (50 mg/kg) either once daily or every 3 day

Application

In murine xenograft models bearing human melanoma cancers (A375), CX-5461 demonstrated significant TGI with TGI equal to 79% on day 32. Human solid tumors grown in murine xenograft models revealed that CX-5461 can be orally administered with favorable pharmacokinetics and an antitumor efficacy. CX-5461 was well tolerated at all tested schedules as judged by the absence of significant changes in animal body weights or overt toxicity.?

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Drygin D, Lin A, Bliesath J, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth[J]. Cancer research, 2011, 71(4): 1418-1430.

Background

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.

In vivo, CX-5461 has shown to suppress tumor volume in both MIA Paca-2 and A375 derived xenograft mice models [1].

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

Chemical Properties

Cas No. 1138549-36-6 SDF
Synonyms CX 5461;CX5461
Chemical Name 2-(4-methyl-1,4-diazepan-1-yl)-N-[(5-methylpyrazin-2-yl)methyl]-5-oxo-[1,3]benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxamide
Canonical SMILES CC1=CN=C(C=N1)CNC(=O)C2=C3N(C4=CC=CC=C4S3)C5=C(C2=O)C=CC(=N5)N6CCCN(CC6)C
Formula C27H27N7O2S M.Wt 513.61
Solubility 2 mg/mL in DMF (ultrasound for 5 minutes and heat to 40 ℃) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.947 mL 9.735 mL 19.47 mL
5 mM 0.3894 mL 1.947 mL 3.894 mL
10 mM 0.1947 mL 0.9735 mL 1.947 mL
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3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

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Average Rating: 5 ★★★★★ (Based on Reviews and 27 reference(s) in Google Scholar.)

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