CX-5461 (Synonyms: CX 5461;CX5461) |
| رقم الكتالوجGC14404 |
CX-5461 هو مثبط قوي وشفوي لتخليق الرنا الريباسيإنه يمنع نسخ الرنا الريباسي الذي يحركه البوليميراز I مع IC50s من 142 و 113 و 54 نانومتر في خلايا HCT-116 و A375 و MIA PaCa-2 ، على التوالي
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.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
CX-5461 is a potent and oral rRNA synthesis inhibitor. It inhibits RNA polymerase I-driven transcription of rRNA with IC50s of 142, 113, and 54 nM in HCT-116, A375, and MIA PaCa-2 cells, respectively[1]. CX-5461 is a DNA G-quadruplex stabilizer that is selectively lethal to BRCA1/2-deficient tumors[2].
In vitro, CX-5461 (2µM) was used to treat 50 human cancer cell lines and 5 non-transformed cell lines. The median EC50 for all cancer cell lines was 147 nM, while the EC50 value for all normal cell lines was approximately 5000nM, indicating that normal cells can tolerate the reduction of rRNA synthesis without inducing cell death[3]. CX-5461 (1.5µM) was used to treat PANC-1 cells for 24h, which inhibited cell migration and increased the expression of cadherin (CDH1) in cells[4]. Treatment of osteosarcoma MNNG and U2-OS cells with CX-5461 (0.01-10 µM) significantly reduced cell viability, induced G2 arrest and expression of microtubule-associated protein 1 light chain 3 II isoform[5].
In vivo, CX-5461 (125 mg/kg) was intraperitoneally injected into mice transplanted with MV 4;11 tumor cells for three weeks and showed effective antitumor activity, induced elevated p21 levels, and was well tolerated[6]. Oral administration of CX-5461 (40 mg/kg) to mice bearing ovarian cancer significantly inhibited tumor growth, reduced tumor volume, and increased γH2AX, a marker of DNA double-strand breaks in tumor cells[7].
References:
[1] Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth[J].Cancer Res. 2011 Feb 15;71(4):1418-30.
[2]Xu H, Di Antonio M, McKinney S, et al. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours[J]. Nature communications, 2017, 8(1): 14432.
[3]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.
[4]El Hassouni B, Mantini G, Immordino B, et al. CX-5461 inhibits pancreatic ductal adenocarcinoma cell growth, migration and induces DNA damage[J]. Molecules, 2019, 24(24): 4445.
[5]Li L, Li Y, Zhao J, et al. CX-5461 induces autophagy and inhibits tumor growth via mammalian target of rapamycin-related signaling pathways in osteosarcoma[J]. OncoTargets and therapy, 2016: 5985-5997.
[6]Bywater M J, Poortinga G, Sanij E, et al. Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53[J]. Cancer cell, 2012, 22(1): 51-65.
[7]Sanij E, Hannan K M, Xuan J, et al. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer[J]. Nature communications, 2020, 11(1): 2641.
| Cell experiment [1]: | |
Cell lines | 50 human cancer cell lines and 5 nontransformed cell lines |
Preparation Method | Cells were treated with 2μM of CX-5461 for 1 hour and chromatin immunoprecipitation (ChIP) assay was performed. |
Reaction Conditions | 2µM; 1h |
Applications | The median EC50 across all tested cell lines was 147 nM, yet all normal cell lines had EC50 values of approximately 5000 nM. |
| Animal experiment [2]: | |
Animal models | CrTac:Ncr-Foxn1nu mice |
Preparation Method | Xenografts were initiated by subcutaneous injection of MV 4;11 cells into the right hind flank region of each mouse. When tumors reached a designated volume of ∼150mm3, animals were randomized and divided into Vehicle (50 mM NaH2PO4, pH 4.5) or CX-5461 treatment groups of 10 mice per group. CX-5461 was administered intraperitoneally once a week at 125 mg/kg for the length of 25 days. |
Dosage form | 125mg/kg; i.p. |
Applications | CX-5461 exhibited potent antitumor activity, induced increased levels of p21, and was well tolerated. |
References: | |
| Cas No. | 1138549-36-6 | SDF | |
| المرادفات | 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 |
| الذوبان | 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 | 389.4 μL | 1.947 mL | 3.894 mL |
| 10 mM | 194.7 μL | 973.5 μL | 1.947 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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 *