1. Cell Cycle/DNA Damage
  2. DNA/RNA Synthesis

CX-5461 

Cat. No.: HY-13323 Purity: 98.47%
Handling Instructions

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

CX-5461 Chemical Structure

CAS No. : 1138549-36-6

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Free Sample (0.5-1 mg)   Apply now  
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
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Customer Review

Other Forms of CX-5461:

    CX-5461 purchased from MCE. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540.

    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 MCE. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540.

    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 MCE. Usage Cited in: Oncotarget. 2017 Oct 29;8(57):96536-96552.

    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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    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.

    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].

    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].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    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
    *Please refer to the solubility information to select the appropriate solvent.
    References
    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), gemcitabine, or CX-5461 treatment groups. Tumor growth inhibition (TGI) is determined on the last day of study according to the formula: TGI (%)=[100 − (VfD− ViD)/ (VfV − ViV) × 100], where ViV is the initial mean tumor volume in vehicle-treated group, VfV is the final mean tumor volume in vehicle-treated group, ViD is the initial mean tumor volume in drug-treated group, and VfD 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
    Molecular Weight

    513.61

    Formula

    C₂₇H₂₇N₇O₂S

    CAS No.

    1138549-36-6

    SMILES

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

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 98.47%

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    Product Name:
    CX-5461
    Cat. No.:
    HY-13323
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    CX-5461

    Cat. No.: HY-13323