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.
Cas No.: 1138549-36-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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
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. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Average Rating: 5
(Based on Reviews and 27 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *