Ponatinib (AP24534) is a imidazopyridine-based pan-inhibitor of the kinases Abl, Abl(T315I), and other clinically important Abl kinase domain mutants at potencies of 0.37 nM, 2.0 nM, and 0.30-0.44 nM, respectively. Ponatinib also potently inhibits Src, VEGFR, FGFR, and PDGFR at 5.4, 1.5, 22, and 1.1 nM, respectively, while being >1000-fold selective over IGF-1R, Aurora A, andCDK2/Cyclin E. [1] In contrast to first- (imatinib) and second-line therapies (nilotinib, dasatinib) for CML, Ponatinib shows inhibition against the T31I mutant of Bcr-Abl.
In a panel of leukemic cell lines containing activating mutations in Flt3, Kit, or activating fusions of FGFR, PDGFRa, EOL1, and KG-1, Ponatinib inhibited phosphorylation of all four receptor tyrosine kinases in a dose dependent manner with IC50 values between 0.3 and 20 nM. [2] Apoptotic induction is believed to be the mechanism by which Ponatinib inhibits FLT3-ITD to in turn inhibit MV4-11 cell viability. [2]
Technical information:
| Chemical Formula: | C29H27F3N6O | |
| CAS #: | 943319-70-8 | |
| Molecular Weight: | 532.57 | |
| Purity: | >98% | |
| Appearance: | White | |
| Chemical Name: | 3-(2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | AP-24534, AP24534, Ponatinib |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | O'Hare et al., AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Res. 2009, 16(5), 401-412. Pubmed ID: 19878872 |
| 2. | Gozgit et al., Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol. Cancer. Ther. 2011, 10, 1028-1035. Pubmed ID: 21482694 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
