CX-5461 dihydrochloride

Cat. No.: HY-13323A Purity: 98.18%: FAQs
Data Sheet SDS COA Handling Instructions

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.

CX-5461 dihydrochloride Chemical Structure

Size	Price	Stock	Quantity
5 mg	USD 120	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 192	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 552	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 880	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 27 publication(s) in Google Scholar

Other Forms of CX-5461 dihydrochloride:

CX-5461 In-stock

24 Publications Citing Use of MCE CX-5461 dihydrochloride

: CX-5461 dihydrochloride purchased from MCE. 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 MCE. 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 MCE. 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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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].

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].

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

Clinical Trial

Molecular Weight

586.54

Appearance

Solid

Formula

C₂₇H₂₉Cl₂N₇O₂S

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, 6 months; -20°C, 1 month (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	---	---	---

*Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: PBS
Solubility: 6.25 mg/mL (10.66 mM); Clear solution; Need ultrasonic and warming and heat to 60°C

*All of the co-solvents are available by MCE.

Purity & Documentation

Purity: 98.18%

Select Batch:

Data Sheet (283 KB) SDS (251 KB)

COA (258 KB) HNMR (321 KB) RP-HPLC (210 KB) LCMS (265 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]