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AP24534

Cat. No. M1648
AP24534 Structure
Synonym:

Ponatinib

Size Price Availability Quantity
10mg USD 50 In stock
50mg USD 100 In stock
100mg USD 130 In stock
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Quality Control
Biological Activity

Ponatinib (AP24534) is a novel potent BCR-ABL or BCR-ABLT3151 with an IC50 values of 0.37 and 2.0 nM, respectively. Ponatinib (AP24534) also inhibits other ABL kinase domain mutants at nanomolar potencies. AP24534 exhibits inhibitory activity against PDGFRα, c-Src and c-Kit (IC50 values are 1.1, 5.4 and 12.5 nM respectively) potently inhibits FGFR and VEGFR family kinases.

Protocol
Cell Experiment
Cell lines MV4-11, Kasumi-1, KG1, and EOL1 cells
Preparation method Cell viability assays.
Cell viability was assessed using the Cell Titer 96 Aqueous One Solution Cell Proliferation Assay. Exponentially growing cell lines were plated into 96-well plates and incubated overnight at 37°C. Twenty-four hours after plating, cells were treated with compound or vehicle (dimethyl sulfoxide) for 72 hours. Absorbance was measured using a Wallac Victor microplate reader (PerkinElmer). Data are plotted as percent viability relative to vehicle-treated cells and the IC50 values (the concentration that causes 50% inhibition) are calculated using XLfit version 4.2.2 for Microsoft Excel. Data are shown as mean (±SD) from 3 separate experiments, each tested in triplicate.
Concentrations 0~100 nM
Incubation time 72 h
Animal Experiment
Animal models MV4-11 human tumor subcutaneous xenograft model
Formulation aqueous 25 mmol/L citrate buffer (pH = 2.75)
Dosages 1, 2.5, 5, 10, and 25 mg/kg/d once daily for 4 weeks
Administration orally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 532.56
Formula C29H27F3N6O
CAS Number 943319-70-8
Purity 100.00%
Solubility DMSO ≥100 mg/mL
Ethanol ≥100 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Transl Stroke Res. (2017). Figure 7. Ponatinib (Abmole Bioscience, China)
Method i.g.
Cell Lines rat
Concentrations 20 mg/kg
Incubation Time 24 h
Results Compared with sham group, the protein expressions of RIPK1, RIPK3, andMLKL in the rat brains were up-regulated in the I/R group, which were suppressed by ponatinib alone or combination with emricasan, whereas emricasan alone had no effect on the expressions of RIPK1, RIPK3, and MLKL (Fig. 7).
Rating
Source Transl Stroke Res. (2017). Figure 6. Ponatinib (Abmole Bioscience, China)
Method i.g.
Cell Lines rat
Concentrations 20 mg/kg
Incubation Time 24 h
Results Compared with the sham group, there were significant increases in the caspase-3 and caspase-8 activities in the I/R-treated rat brains; these increases were obviously blocked in the presence of emricasan alone or together with ponatinib, whereas ponatinib alone did not affect the caspase-3 and caspase-8 activities (Fig. 6).
Rating
Source Transl Stroke Res. (2017). Figure 5. Ponatinib (Abmole Bioscience, China)
Method i.g.
Cell Lines rat
Concentrations 20 mg/kg
Incubation Time 24 h
Results As displayed in Fig. 5, consistent with the results before, emricasan or ponatinib alone could reduce the neurological deficit score and infarct volume in the I/R-treated rats; these effects were obviously enhanced upon the combined application of emricasan and ponatinib.
Rating
Source Transl Stroke Res. (2017). Figure 4. Ponatinib (Abmole Bioscience, China)
Method i.g.
Cell Lines rat
Concentrations 20 mg/kg
Incubation Time 24 h
Results As shown in Fig. 4, the neurological deficit score and infarct volume were obviously decreased in the presence of emricasan (A and B) or ponatinib (C and D) compared to that in the I/R group, whereas the vehicle of emricasan or ponatinib has no such effects.
Rating
Source Transl Stroke Res. (2017). Figure 3. Ponatinib (Abmole Bioscience, China)
Method i.g.
Cell Lines rat
Concentrations 20 mg/kg
Incubation Time 24 h
Results Cerebral I/R caused dramatic increases in neurological deficit score and infarct volume; these increases were attenuated by pretreatment with emricasan (A and B) or ponatinib (C and D), whereas the vehicle of emricasan or ponatinib did not show such effects.
Rating
Product Citations
References

Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.
Chase et al. Haematologica. 2012 Aug 8. PMID: 22875613.

Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities.
Ren et al. Leukemia. 2012 Jul 11. PMID: 22781593.

The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the multidrug resistance-associated ATP-binding cassette transporter ABCG2.
Sen et al. Mol Cancer Ther. 2012 Jul 9. PMID: 22778153.

Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases.
Lierman et al. Leukemia. 2012 Jul;26(7):1693-5. PMID: 22301675.

Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.
Gozgit JM, et al. Mol Cancer Ther. 2011 Jun;10(6):1028-35. PMID: 21482694.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AP24534, Ponatinib supplier, Src-bcr-Abl, inhibitors

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