2. Protein Tyrosine Kinase/RTK Autophagy
  3. Bcr-Abl PDGFR VEGFR FGFR Src Autophagy
  4. Ponatinib

Ponatinib (AP24534) is an orally active multi-targeted kinase inhibitor with IC50s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.

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

Ponatinib Chemical Structure

Ponatinib Chemical Structure

CAS No. : 943319-70-8

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 73 In-stock
Solution
10 mM * 1 mL in DMSO USD 73 In-stock
Solid
5 mg USD 42 In-stock
10 mg USD 66 In-stock
50 mg USD 99 In-stock
100 mg USD 158 In-stock
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Customer Review

Based on 30 publication(s) in Google Scholar

Other Forms of Ponatinib:

Ponatinib Related Antibodies

Top Publications Citing Use of Products

    Ponatinib purchased from MedChemExpress. Usage Cited in: Exp Hematol. 2014 May;42(5):369-379.e3.  [Abstract]

    (B,D) Phosphorylation levels of F/P (or its mutant), STAT5, or ERK in lysates of CMPs expressing Hes1 with F/P, F/P-D842V, or F/P-T674I, which have been treated with indicated doses of (B) Imatinib or (D) Ponatinib for 15 min. Data are representative of three independent experiments.

    View All PDGFR Isoform Specific Products:

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    PDGFR PDGFRβ PDGFRα

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    VEGFR1/Flt-1 VEGFR2/KDR/Flk-1 VEGFR3/Flt-4

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    FGFR FGFR1 FGFR2 FGFR3 FGFR4 FGF21

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    Lck Fyn Blk

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Ponatinib (AP24534) is an orally active multi-targeted kinase inhibitor with IC50s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively[1].

    IC50 & Target[1]

    VEGFR2

    1.5 nM (IC50)

    PDGFRα

    1.1 nM (IC50)

    FGFR1

    2.2 nM (IC50)

    c-Kit

    12.5 nM (IC50)

    In Vitro

    Ponatinib (AP24534) potently inhibits native ABL (IC50: 0.37 nM), ABLT315I (IC50: 2.0 nM), and other clinically important ABL kinase domain mutants (IC50: 0.30-0.44 nM). Ponatinib also inhibits SRC (IC50: 5.4 nM) and members of the VEGFR, FGFR, and PDGFR families of receptor tyrosine kinases. Ponatinib potently inhibits proliferation of Ba/F3 cells expressing native BCR-ABL (IC50: 0.5 nM). All BCR-ABL mutants tested remained sensitive to Ponatinib (IC50: 0.5-36 nM) including BCR-ABLT315I (IC50: 11 nM)[1].
    Ponatinib inhibits the in vitro kinase activity of FLT3, KIT, FGFR1, and PDGFRα with IC50 values of 13, 13, 2, and 1 nM, respectively. Ponatinib inhibits phosphorylation of all 4 RTKs in a dose-dependent manner, with IC50 values between 0.3 to 20 nM. Consistent with these activated receptors being important in driving leukemogenesis Ponatinib also potently inhibits the viability of all 4 cell lines with IC50 values of 0.5 to 17 nM. In contrast, the IC50 for inhibition of RS4;11 cells which express native (unmutated) FLT3, is more than 100 nM[2].

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

    Ponatinib Related Antibodies
    In Vivo

    In a survival model in which mice are instead injected with Ba/F3 BCR-ABLT315I cells, administration of Dasatinib at doses as high as 300 mg/kg has no effect on survival time. By contrast, treatment with Ponatinib (AP24534) prolongs survival in a dose-dependent manner. Ponatinib dosed orally for 19 days at 5, 15, and 25 mg/kg prolongs median survival to 19.5, 26, and 30 days, respectively compare to 16 days for vehicle-treated mice (p<0.01 for all three dose levels). The anti-tumor activity of Ponatinib (AP24534) is further assessed in a xenograft model in which Ba/F3 BCR-ABLT315I cells are injected subcutaneously into mice. Tumor growth is inhibited by Ponatinib in a dose-dependent manner compare to vehicle-treated mice, with significant suppression of tumor growth upon daily oral dosing at 10 and 30 mg/kg (%T/C = 68% and 20%, respectively; p<0.01 for both dose levels). Daily oral dosing of 50 mg/kg Ponatinib causes significant tumor regression (%T/C = 0.9%, p<0.01), with a 96% reduction in mean tumor volume at the final measurement compared to the start of treatment. Ponatinib is well tolerated at all efficacious dose levels for the duration of the study; maximal decreases in body weight are <5%, <5%, and <12% for the 10, 30, and 50 mg/kg dose groups, respectively, with no signs of overt toxicity[1].
    Ponatinib (1-25 mg/kg) is administered orally, once daily for 28 days, to mice bearing MV4-11 xenografts. Ponatinib potently inhibits tumor growth in a dose-dependent manner. Administration of 1 mg/kg, the lowest dose tested, leads to significant inhibition of tumor growth (TGI=46%, P<0.01) and doses of 2.5 mg/kg or greater results in tumor regression[2].

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

    532.56

    Formula

    C29H27F3N6O
    CAS No.
    Appearance

    Solid

    Color

    Light yellow to yellow

    SMILES

    CC1=C(C=C(C=C1)C(NC2=CC(C(F)(F)F)=C(C=C2)CN3CCN(CC3)C)=O)C#CC4=CN=C5N4N=CC=C5
    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: 

    1M HCl : 50 mg/mL (93.89 mM; ultrasonic and adjust pH to 1 with HCl)

    DMSO : 25 mg/mL (46.94 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.8777 mL 9.3886 mL 18.7772 mL
    5 mM 0.3755 mL 1.8777 mL 3.7554 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.

    • Molarity Calculator

    • Dilution Calculator

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

    Mass
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    Concentration
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    Volume
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    Molecular Weight *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    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:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock 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).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.43%

    COA (252 KB) LCMS (95 KB) Elemental Analysis Report (110 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [1]

    Ba/F3 cell lines are distributed in 96-well plates (4×103 cells/well) and incubated with escalating concentrations of Ponatinib for 72 hr. The inhibitor ranges used are: 0-625 nM for cells expressing BCR-ABL and 0-10,000 nM for BCR-ABL negative cells. Proliferation is measured using a methanethiosulfonate (MTS)-based viability assay. IC50 values are reported as the mean of three independent experiments performed in quadruplicate. For cell proliferation experiments with CML or normal primary cells, mononuclear cells are plated in 96-well plates (5×104 cells/well) over graded concentrations of Ponatinib (0-1000 nM) in RPMI supplemented with 10% FBS, L-glutamine, penicillin/streptomycin, and 100 μM β-mercaptoethanol. Following a 72 hr incubation, cell viability is assessed by subjecting cells to an MTS assay[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice[1]
    For Ba/F3 survival model, Ba/F3 cells expressing native BCR-ABL or BCR-ABLT315I are injected into the tail vein of female SCID mice (100 μL of a 1×107 cells/mL suspension in serum-free medium). Beginning 72 hr later mice are treated once daily by oral gavage with vehicle (25 mM citrate buffer, pH 2.75), Ponatinib, or Dasatinib for up to 19 consecutive days. Moribund animals are sacrificed as per IACUC guidelines. On necropsy, mice have marked splenomegaly due to tumor cell infiltration. Survival data are analyzed using Kaplan-Meier method, and statistical significance is evaluated with a Log-rank test comparing the survival time of each treatment group with the vehicle group. For Ba/F3 Tumor Model, Ba/F3 BCR-ABLT315I cells are implanted subcutaneously into the right flank of female nude mice (100 μL of a 1×107 cells/mL cell suspension in serum-free medium). Mice are randomized to treatment groups when the average tumor volume reaches approximately 500 mm3. Mice are treated once daily by oral gavage with vehicle (25 mM citrate buffer, pH 2.75) or Ponatinib for up to 19 consecutive days. Tumor volume (mm3) is calculated. To determine tumor growth inhibition when the treatment period is finished, mean tumor volume for treatment group/mean tumor volume for control group (%T/C) is calculated at the final measurement.

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

    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.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO / 1M HCl 1 mM 1.8777 mL 9.3886 mL 18.7772 mL 46.9431 mL
    5 mM 0.3755 mL 1.8777 mL 3.7554 mL 9.3886 mL
    10 mM 0.1878 mL 0.9389 mL 1.8777 mL 4.6943 mL
    15 mM 0.1252 mL 0.6259 mL 1.2518 mL 3.1295 mL
    20 mM 0.0939 mL 0.4694 mL 0.9389 mL 2.3472 mL
    25 mM 0.0751 mL 0.3755 mL 0.7511 mL 1.8777 mL
    30 mM 0.0626 mL 0.3130 mL 0.6259 mL 1.5648 mL
    40 mM 0.0469 mL 0.2347 mL 0.4694 mL 1.1736 mL
    1M HCl 50 mM 0.0376 mL 0.1878 mL 0.3755 mL 0.9389 mL
    60 mM 0.0313 mL 0.1565 mL 0.3130 mL 0.7824 mL
    80 mM 0.0235 mL 0.1174 mL 0.2347 mL 0.5868 mL
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    Ponatinib 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:

    Ponatinib943319-70-8AP24534AP 24534AP-24534Bcr-AblPDGFRVEGFRFGFRSrcAutophagyPlatelet-derived growth factor receptorVascular endothelial growth factor receptorFibroblast growth factor receptororallyactivemulti-targetedkinaseAblPDGFRαVEGFR2FGFR1Inhibitorinhibitorinhibit

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