| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Ponatinib (formerly known as AP24534; trade name Iclusig) is a novel, orally bioavailable multi-targeted kinase inhibitor with potent antitumor activity. In cell-free experiments, it suppresses Abl, PDGFRα, VEGFR2, FGFR1, and Src with IC50 values of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM, respectively. It may be used to treat acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) in patients who have the Philadelphia chromosome (Ph+). Ponatinib inhibits Bcr-Abl in both its unmutated and mutated forms, including T315I, a missense mutation that makes Bcr-Abl extremely resistant to drug therapy. On December 14, 2012, the US FDA approved ponatinib for use in patients with Ph+ ALL and CML that was resistant or intolerant.
| Targets |
VEGFR2 (IC50 = 1.5 nM); PDGFRα (IC50 = 1.1 nM); FGFR1 (IC50 = 2.2 nM); c-Kit (IC50 = 12.5 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The impact of AP24534 (0-320 nM) on the activity of GST-Abl kinase is measured with a synthetic peptide substrate (Abltide: EAIYAAPFAKKK). In 25 μL reaction mixture, assays are run for 15 minutes at 30 °C. 8 mM MOPS (pH 7), 0.2 mM EDTA, 50 μM Abltide, 30 mM MgCl2, 10 mM β-glycerol phosphate, 1 mM EGTA, 0.002% Brij-35, 0.4 mM DTT, 0.2 mg/mL BSA, 0.4 mM sodium orthovanadate, 10 nM WT or mutant GST-Abl kinase, and 100 µM ATP/γ-32[P]ATP (5000 cpm/pmol). An immersion in 0.75% phosphoric acid is required to stop a reaction after part of the reaction mixture has been transferred onto a p81 phosphocellulose filter. Phosphate incorporation is measured using scintillation counting; filters are air dried after three rounds of washing in 0.75% phosphoric acid and rinsing in acetone. By removing the peptide substrate from the kinase reaction, background binding to the filters is taken into account for all results. Kinase assays come before time course experiments to determine the linear range of enzymatic activity.
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| Cell Assay |
Ba/F3 cell lines are arranged in 96-well plates (4 × 103 cells/well) and given a 72-hour incubation period with AP24534. A methanethiosulfonate (MTS)-based viability assay (CellTiter96 Aqueous One Solution) is used to measure proliferation. Every value is compared to the drug-free control wells. The mean of three separate, quadruplicat experiments is used to report IC50 values.
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| Animal Protocol |
Mice: In the Ba/F3 survival model, 100 μL of a 1×107 cells/mL suspension in serum-free medium is injected into the tail vein of female SCID mice expressing native BCR-ABL or BCR-ABLT315I. Mice are treated with vehicle (25 mM citrate buffer, pH 2.75), dasatinib, or ponatinib once daily for up to 19 days in a row starting 72 hours later. IACUC guidelines are followed when sacrificing morbid animals. Mice with evident splenomegaly from tumor cell infiltration were found during necropsy. The Kaplan-Meier method is utilized to analyze the survival data, and a Log-rank test is employed to assess statistical significance by comparing the survival time of each treatment group with that of the vehicle group. Ba/F3 BCR-ABLT315I cells, 100 μL of a 1×107 cells/mL cell suspension in serum-free medium, are subcutaneously inserted into the right flank of female nude mice for the Ba/F3 Tumor Model. The mice are assigned to treatment groups at random once the tumor volume averages around 500 mm3. For a maximum of 19 days, mice are given oral gavage once a day with either vehicle (25 mM citrate buffer, pH 2.75) or ponatinib. It computes the tumor volume (mm3). At the final measurement, mean tumor volume for treatment group/mean tumor volume for control group (%T/C) is calculated to determine tumor growth inhibition when the treatment period is over.
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| References |
| Molecular Formula |
C29H27F3N6O
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| Molecular Weight |
532.56
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| Exact Mass |
532.22
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| Elemental Analysis |
C, 65.40; H, 5.11; F, 10.70; N, 15.78; O, 3.00
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| CAS # |
943319-70-8
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| Related CAS # |
Ponatinib hydrochloride;1114544-31-8;Ponatinib-d8;1562993-37-6
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| Appearance |
white solid powder
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| SMILES |
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
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| InChi Key |
PHXJVRSECIGDHY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
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| Chemical Name |
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
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| Synonyms |
AP-24534; AP24534; Ponatinib; AP 24534; Trade name: Iclusig
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 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 | |
| 10 mM | 0.1878 mL | 0.9389 mL | 1.8777 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03690115 | Active Recruiting |
Drug: Ponatinib 30 MG | Leukemia, Myeloid, Acute | Versailles Hospital | December 2, 2019 | Phase 2 |
| NCT02467270 | Active Recruiting |
Drug: Ponatinib | Myeloid Leukemia, Chronic, Chronic Phase |
Takeda | June 30, 2015 | Phase 2 |
| NCT04554459 | Active Recruiting |
Drug: Ponatinib 15 MG Oral Tablet | Ph+ ALL Newly Diagnosed |
Institute of Hematology and Blood Transfusion, Czech Republic |
February 16, 2021 | Phase 2 |
| NCT03934372 | Recruiting | Drug: Ponatinib | Leukemia Lymphoma |
Incyte Biosciences International Sàrl |
January 29, 2020 | Phase 1 Phase 2 |
| NCT05306301 | Completed | Drug: Ponatinib | Leukemia, Acute Lymphoblastic Chemotherapy |
Gruppo Italiano Malattiec EMatologiche dell'Adulto |
October 5, 2022 | Phase 2 |
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