Shelf life (days): 1460.0
Formulation: A solid
Formal Name: 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl-2,2,3,3,5,5,6,6-d8)methyl]-3-(trifluoromethyl)phenyl]-benzamide
Purity: ≥99% deuterated forms (d1-d8)
Formula Markup: C29H19D8F3N6O
Formula Weight: 540.608209
CAS Number: 1562993-37-6
Notes: Ponatinib-d8 is intended for use as an internal standard for the quantification of ponatinib (Item No. 11494) by GC- or LC-MS. Ponatinib is an orally bioavailable Bcr-Abl tyrosine kinase inhibitor (IC50 = 0.37 nM).{25003} It inhibits the tyrosine kinase inhibitor-resistant mutant Bcr-AblT315I (IC50 = 2 nM), as well as Bcr-AblQ252H, Bcr-AblY253F, Bcr-AblM351T, and Bcr-AblH396P mutants (IC50s = 0.44, 0.3, 0.3, and 0.34 nM, respectively). It is selective for Bcr-Abl and these mutants over the insulin receptor, IGF-1R, Aurora A kinase, and Cdk2/cyclin E but does inhibit the receptor tyrosine kinases c-Src, VEGF receptor 2 (VEGFR2), FGFR1, and PDGFRα (IC50s = 5.4, 1.5, 2.2, and 1.1 nM, respectively). Ponatinib inhibits proliferation of Ba/F3 cells expressing native (IC50 = 0.5 nM) or mutant Bcr-Abl (IC50s = 0.5-36 nM) and induces apoptosis. It reduces tumor growth in a Ba/F3 Bcr-AblT315I mouse xenograft model when administered at doses ranging from 10 to 30 mg/kg. Formulations containing ponatinib have been used in the treatment of chronic-, accelerated-, or blast-phase chronic myeloid leukemia (CML), T315I-positive CML, or T315I-positive Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
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