CX-5461 dihydrochloride

Name: CX-5461 dihydrochloride
Brand: MedChemExpress
SKU: HY-13323A
Rating: 5.0 (66 reviews)

Cat. No.: HY-13323A Purity: 99.41%: Data Sheet
COA

SDS
Handling Instructions
FAQs
Technical Support

CX-5461 dihydrochloride 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).

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

Size	Stock	Quantity
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
500 mg	Get quote

or Bulk Inquiry

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 66 publication(s) in Google Scholar

Other Forms of CX-5461 dihydrochloride:

CX-5461 In-stock

66 Publications Citing Use of MCE CX-5461 dihydrochloride

: CX-5461 dihydrochloride 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 dihydrochloride 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 dihydrochloride 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.

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All DNA/RNA Synthesis Isoform Specific Products:

View All Isoforms

RNASE L DNA Polymerases RNA Polymerases Helicases DNA Ligase

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

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]

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.

Molecular Weight

586.54

Formula

C₂₇H₂₉Cl₂N₇O₂S

Appearance

Solid

Color

Light yellow to yellow

SMILES

[H]Cl.CC1=NC=C(CNC(C2=C3N(C4=NC(N5CCN(CCC5)C)=CC=C4C2=O)C6=C(S3)C=CC=C6)=O)N=C1.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

H₂O : 5 mg/mL (8.52 mM; ultrasonic and warming and heat to 80°C)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.7049 mL	8.5246 mL	17.0491 mL
5 mM	0.3410 mL	1.7049 mL	3.4098 mL
10 mM	---	---	---

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 (sealed storage, away from moisture). 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.

Molarity Calculator
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 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

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: 99.41%

Select Batch:

Data Sheet (281 KB) SDS (252 KB)

COA (256 KB) HNMR (323 KB) LCMS (102 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. [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. [Content Brief]

Complete Stock Solution Preparation Table

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

H₂O	1 mM	1.7049 mL	8.5246 mL	17.0491 mL	42.6228 mL
H₂O	5 mM	0.3410 mL	1.7049 mL	3.4098 mL	8.5246 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.