1. MAPK/ERK Pathway
  2. Raf
  3. PLX-4720

PLX-4720 

Cat. No.: HY-51424 Purity: 99.73%
Handling Instructions

PLX-4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.

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

PLX-4720 Chemical Structure

PLX-4720 Chemical Structure

CAS No. : 918505-84-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 66 In-stock
Estimated Time of Arrival: December 31
5 mg USD 60 In-stock
Estimated Time of Arrival: December 31
10 mg USD 84 In-stock
Estimated Time of Arrival: December 31
25 mg USD 132 In-stock
Estimated Time of Arrival: December 31
50 mg USD 180 In-stock
Estimated Time of Arrival: December 31
100 mg USD 288 In-stock
Estimated Time of Arrival: December 31
200 mg USD 528 In-stock
Estimated Time of Arrival: December 31
500 mg   Get quote  
1 g   Get quote  

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Customer Review

Top Publications Citing Use of Products

    PLX-4720 purchased from MCE. Usage Cited in: J Clin Invest. 2018 Aug 31;128(9):3976-3990.

    NRP1 expression assessed by immunoblotting in parental and PLX-4720-resistant A375 cells transfected with pre-miRNA-338 (or mock transfected).

    View All Raf Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    PLX-4720 is a potent and selective inhibitor of B-RafV600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), and 10-fold selectivity for B-RafV600E than wild-type B-Raf.

    IC50 & Target

    B-RafV600E

    13 nM (IC50)

    B-Raf

    160 nM (IC50)

    BRK

    130 nM (IC50)

    FRK

    1300 nM (IC50)

    Csk

    1500 nM (IC50)

    Src

    1700 nM (IC50)

    FAK

    1700 nM (IC50)

    FGFR

    1900 nM (IC50)

    KDR

    2300 nM (IC50)

    HGK

    2800 nM (IC50)

    CSF1R

    3300 nM (IC50)

    Aurora A

    3400 nM (IC50)

    In Vitro

    PLX-4720 displays >10 times selectivity against wild type B-Raf, and >100 times selectivity over other kinases such as Frk, Src, Fak, FGFR, and Aurora A with IC50 of 1.3-3.4 μM. PLX-4720 significantly inhibits the ERK phosphorylation in cell lines bearing B-RafV600E with IC50 of 14-46 nM, but not the cells with wild-type B-Raf. PLX-4720 significantly inhibits the growth of tumor cell lines bearing the B-RafV600E oncogene, such as COLO205, A375, WM2664, and COLO829 with GI50 of 0.31 μM, 0.50 μM, 1.5 μM, and 1.7 μM, respectively. In addition, PLX-4720 treatment at 1 μM induces cell cycle arrest and apoptosis exclusively in the B-RafV600E-positive 1205Lu cells, but not in the B-Raf wild-type C8161 cells[1]. PLX-4720 treatment (10 μM) significantly induces > 14-fold expression of BIM in the PTEN+ cells, compared with the PTEN- cell lines (4-fold), giving an explanation of the resistance of PTEN- cells to PLX-4720-induced apoptosis[2].

    In Vivo

    Oral administration of PLX-4720 at 20 mg/kg/day induces significant tumor growth delays and regressions in B-RafV600E-dependent COLO205 tumor xenografts, without obvious adverse effects in mice even at dose of 1 g/kg. PLX-4720 at 100 mg/kg twice daily almost completely eliminates the 1205Lu xenografts bearing B-RafV600E, while has no activity against C8161 xenografts bearing wild-type B-Raf. The anti-tumor effects of PLX-4720 correlate with the blockade of MAPK pathway in those cells harboring the V600E mutation[1]. PLX-4720 treatment at 30 mg/kg/day significant inhibits the tumor growth of 8505c xenografts by >90%, and dramatically decreases distant lung metastases[3].

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 50 mg/mL (120.82 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4165 mL 12.0823 mL 24.1645 mL
    5 mM 0.4833 mL 2.4165 mL 4.8329 mL
    10 mM 0.2416 mL 1.2082 mL 2.4165 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 5 mg/mL (12.08 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 5 mg/mL (12.08 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    For each enzyme (0.1 ng), 20-μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% Tween-20, 100 nM biotin-MEK protein, various ATP concentrations, and increasing concentrations of PLX-4720 at room temperature. Reactions are stopped at 2, 5, 8, 10, 20, and 30 minutes with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, and 0.3% BSA. The stop solution also includes phospho-MEK Antibody, Streptavidin-coated Donor beads and Protein A Acceptor beads from the AlphaScreen Protein A Detection Kit. The antibody and beads are preincubated in stop solution in the dark at room temperature for 30 minutes. The final dilution of antibody is 1/2,000, and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour then are read on a PerkinElmer AlphaQuest reader.

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

    Cell Assay
    [1]

    Cells are treated with various concentrations PLX-4720 for 24, 48, and 72 hours. Cell proliferation is measured by using the CellTiter-Glo Luminescent Cell Viability Assay or MTT assay. For cell cycle analysis, supernatant and cells are collected, pelleted, and fixed with 70% ethanol. Before staining with propidium iodide (10 μg/mL), cells are incubated for 1 hour at 37°C in 0.5 mg/mL RNase I to rid samples of residual RNA contamination. Samples are then analyzed by using the EPICS XL apparatus. For the assessment of apoptosis, media and cells are harvested and pelleted before staining with annexin-FITC and propidium iodide. Samples are subsequently analyzed by using the EPICS XL apparatus.

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

    Animal Administration
    [1]

    Metastatic melanoma cells (2×106) are s.c. injected into the flanks of SCID mice and allowed appr 2 weeks to reach 0.125 mm3 in volume. Subsequently, the animals receive either 100 mg/kg PLX4720 (oral gavage) or vehicle control twice daily for 15 days. Tumor volume is recorded every 72 h. The average tumor size for each respective group is normalized to the tumor volume at the first day of treatment. After 15 days of treatment, animals are killed and tumors are excised, fixed in formalin, paraffin-embedded, and analyzed by immunohistochemistry.

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

    References
    Molecular Weight

    413.83

    Formula

    C₁₇H₁₄ClF₂N₃O₃S

    CAS No.

    918505-84-7

    SMILES

    O=S(NC1=CC=C(C(C(C2=CNC3=NC=C(C=C23)Cl)=O)=C1F)F)(CCC)=O

    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.73%

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    Product Name:
    PLX-4720
    Cat. No.:
    HY-51424
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    PLX-4720

    Cat. No.: HY-51424