CX-5461

Name: CX-5461
Brand: MedChemExpress
SKU: HY-13323
Rating: 5.0 (38 reviews)

Cat. No.: HY-13323 Purity: 99.49%: FAQs
Data Sheet SDS COA Handling Instructions

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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.

For research use only. We do not sell to patients.

CX-5461 Chemical Structure

CAS No. : 1138549-36-6

Size	Price	Stock	Quantity
Free Sample (0.1 - 0.5 mg)		Apply Now
5 mg	USD 132	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 211	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 500	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 720	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 38 publication(s) in Google Scholar

Other Forms of CX-5461:

CX-5461 dihydrochloride In-stock
CX-5461 (Standard) Get quote

35 Publications Citing Use of MCE CX-5461

: CX-5461 purchased from MedChemExpress. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. [Abstract]; Western blot analysis verifying G2/M phase arrest in 6 cell lines. Treatment with IC₅₀ dosages of CX-5461 shows an increase in expression of pCDC2(tyr15) and Cyclin-B versus untreated controls at 72 hours.

: CX-5461 purchased from MedChemExpress. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. [Abstract]; Western blot analysis shows activation of the pCHK1(ser317) and pCHK2(T68), downstream substrates of ATM and ATR kinases. TP53 wild type cell lines show a subsequent activation of p21 but drug response is independent of TP53 status.

: CX-5461 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Oct 29;8(57):96536-96552. [Abstract]; Protein levels of HCMV IE (IE1:IE72, IE2:IE86) and pp65 are detected by WB analysis in untreated and pre-treated HCMV infected cells 72hpi.

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Protocol
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Description

IC₅₀ & Target

IC50: 54 nM (rRNA synthesis, MIA PaCa-2 cells), 113 nM (rRNA synthesis, A375 cells), 142 nM (rRNA synthesis, HCT-116 cells)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
A2780	IC₅₀	0.12 μM Compound: CX-5461	Antiproliferative activity against human A2780 cells incubated for 4 days by MTT assay Antiproliferative activity against human A2780 cells incubated for 4 days by MTT assay	[PMID: 31803394]

In Vitro

CX-5461 is a potent and orally bioavailable inhibitor of Pol I-mediated rRNA synthesis, with IC₅₀s of 142 nM in HCT-116, 113 nM in A375, and 54 nM in MIA PaCa-2 cells, and shows little or no effect on Pol II (IC₅₀, ≥25 μM). CX-5461 has modest inhibition on DNA replication and protein translation. CX-5461 also exhibits broad antiproliferative activity against a panel of human cancer cell lines, with a mean EC₅₀ of 147 nM, but has minimal effect on viability of nontransformed human cells, with EC₅₀ values of appr 5000 nM. EC₅₀s of CX-5461 for HCT-116, A375, and MIA PaCa-2 cell lines are 167, 58, and 74 nM, respectively. CX-5461 induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process^[1]. Eμ-Myc lymphoma cells from tumor-bearing mice are exquisitely sensitive to CX-5461 with an IC₅₀ of 27.3 nM ± 8.1 nM for Pol I transcription after 1 hr and IC₅₀ of 5.4 nM ± 2.1 nM for cell death after 16 hr. CX-5461 activates p53 via the nucleolar stress response in Eμ-MycLymphoma Cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

CX-5461 displays antitumor activity against human solid tumors in murine xenograft models. CX-5461 (50 mg/kg, p.o.) shows significant MIA PaCa-2 growth inhibition with TGI equal to 69% on day 31 and 79% TGI on A375 on day 32^[1]. CX-5461 (50 mg/kg, p.o.) inhibits the Eμ-Myc tumor cells with 84% repression in Pol I transcription at 1 hr posttreatment in C57BL/6 mice. CX-5461 also induces a rapid reduction in tumor burden in the lymph nodes and a concomitant reduction of spleen size to within the normal range^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

513.61

Formula

C₂₇H₂₇N₇O₂S

CAS No.

1138549-36-6

Appearance

Solid

Color

White to yellow

SMILES

CC1=NC=C(CNC(C2=C3N(C4=NC(N5CCN(CCC5)C)=CC=C4C2=O)C6=C(S3)C=CC=C6)=O)N=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

H₂O : 55.56 mg/mL (108.18 mM; ultrasonic and adjust pH to 2 with HCl)

50 mM sodium phosphate (pH 3.5) : 10 mg/mL (19.47 mM; Need ultrasonic)

DMSO : < 1 mg/mL (insoluble or slightly soluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.9470 mL	9.7350 mL	19.4700 mL
5 mM	0.3894 mL	1.9470 mL	3.8940 mL
10 mM	0.1947 mL	0.9735 mL	1.9470 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 15% Cremophor EL 85% Saline
Solubility: 10 mg/mL (19.47 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.49%

Select Batch:

Data Sheet (283 KB) SDS (392 KB)

COA (257 KB) HNMR (292 KB) RP-HPLC (207 KB) LCMS (94 KB) Elemental Analysis Report (115 KB)

Handling Instructions (2659 KB)

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. Cancer Res. 2011 Feb 15;71(4):1418-30. [Content Brief]

[2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65. [Content Brief]

Cell Assay ^[1]	Cells are plated on 96-well plates and treated the next day with dose response of CX-5461 for 96 hours. Cell viability is determined using Alamar Blue and CyQUANT assays^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] Animal experiments are performed with 5- to 6-week-old female athymic (NCr nu/nu fisol) mice of Balb/c. Mice are inoculated with athymic (NCr nu/nu fisol) mice in 100 μL of cell suspension subcutaneously in the right flank. Tumor measurements are performed by caliper analysis, and tumor volume is calculated using the formula (l×w²)/2, where w=width and l=length in mm of the tumor. established tumors (appr 110-120 mm³) are randomized into vehicle (50 mM NaH₂PO₄, pH 4.5), NSC 613327, or CX-5461 treatment groups. Tumor growth inhibition (TGI) is determined on the last day of study according to the formula: TGI (%)=[100 − (Vf^D− Vi^D)/ (Vf^V − Vi^V) × 100], where Vi^V is the initial mean tumor volume in vehicle-treated group, Vf^V is the final mean tumor volume in vehicle-treated group, Vi^D is the initial mean tumor volume in drug-treated group, and Vf^D is the final mean tumor volume in drug-treated group. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. Cancer Res. 2011 Feb 15;71(4):1418-30. [Content Brief] [2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

50 mM sodium phosphate (pH 3.5) / H₂O	1 mM	1.9470 mL	9.7350 mL	19.4700 mL	48.6751 mL
	5 mM	0.3894 mL	1.9470 mL	3.8940 mL	9.7350 mL
	10 mM	0.1947 mL	0.9735 mL	1.9470 mL	4.8675 mL
	15 mM	0.1298 mL	0.6490 mL	1.2980 mL	3.2450 mL
H₂O	20 mM	0.0974 mL	0.4868 mL	0.9735 mL	2.4338 mL
	25 mM	0.0779 mL	0.3894 mL	0.7788 mL	1.9470 mL
	30 mM	0.0649 mL	0.3245 mL	0.6490 mL	1.6225 mL
	40 mM	0.0487 mL	0.2434 mL	0.4868 mL	1.2169 mL
	50 mM	0.0389 mL	0.1947 mL	0.3894 mL	0.9735 mL
	60 mM	0.0325 mL	0.1623 mL	0.3245 mL	0.8113 mL
	80 mM	0.0243 mL	0.1217 mL	0.2434 mL	0.6084 mL
	100 mM	0.0195 mL	0.0974 mL	0.1947 mL	0.4868 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

CX-5461 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

CX-54611138549-36-6CX5461CX 5461DNA/RNA SynthesisInhibitorinhibitorinhibit

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CX-5461

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35 Publications Citing Use of MCE CX-5461

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Complete Stock Solution Preparation Table

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