P-7022 Ponatinib, Free Base, >99%

Synonyms : [AP 24534]

Related Terms : [Iclusig]

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  • 25 mg
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  • 50 mg
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  • 100 mg
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  • 91
  • 79
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  • 200 mg
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  • 136
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  • 250 mg
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  • 162
  • 141
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  • 500 mg
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  • 244
  • 212
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  • 1 g
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  • 418
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  • 2 g
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  • 700
  • 610
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  • M.W. 532.56
  • C29H27F3N6O
  • [943319-70-8]

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 50 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A.

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  • Ponatinib, also known as AP24534, is a multi-targeted tyrosine kinase inhibitor and is active against T315I and other BCR-ABL mutants. Ponatinib inhibited native BCR-ABL (IC50 = 0.37 nM) and the mutants with IC50 values of 2 nM (T315I); 0.44 nM (Q252H); 0.3 nM (Y253F); 0.3 nM (M351T); and 0.34nM (H396P) in biochemical assays. It also inhibited the growth of Ba/F3 cells with IC50 values of 0.5 nM (Native BCR-ABL), 11 nM (T315I), 2.2 nM (Q252H), 2.8 nM (Y253F), 1.5 nM (M351T), and 1.1 nM (H396P). It suppressed BCR-ABL(T315I)-driven tumor growth in mice and completely overcame resistance in cell-based mutagenesis screens. O'Hare, T., et al. "AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance." Cancer Cell 16: 401-412 (2009).
  • Ponatinib inhibited FGFR-mediated signaling and viability with IC50 values <40 nM in Ba/F3 cells engineered to express activated FGFR 1-4, with substantial selectivity over parental Ba/F3 cells. It also inhibited FGFR-mediated signaling with IC50 values <40 nM and inhibited cell growth with GI50 values of 7 to 181 nM in a panel of 14 cell lines representing multiple tumor types (endometrial, bladder, gastric, breast, lung, and colon) and containing dysregulated FGFRs. Ponatinib treatment reduced tumor growth and inhibited signaling in all three mouse tumor models examined. Gozgit, J.M., et al. "Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models." Mol. Cancer Ther. 11: 690-699 (2012).
  • In a pivotal phase 2 trial, ponatinib had substantial activity in heavily pretreated patients and those with refractory T315I. Response rates continued to improve with longer follow-up. Cortes, J.E., et al. "PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation." J. Clin. Oncology 2012 ASCO Annual Meeting Proceedings (Post-Meeting Edition) 30: 6503 (2012).
  • Ponatinib is the active ingredient in the drug product sold under the trade name Iclusig®. This drug is currently approved in at least one country for use in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). NOTE: THE PONATINIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ICLUSIG®, AND IS NOT FOR HUMAN USE.
  • Related CAS numbers: 1114544-31-8 for the Ponatinib HCl salt.
  • Another CAS number previously assigned to Ponatinib, Free Base, namely 952306-26-2, has been deleted by CAS and is no longer in use.
  • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
  • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
  • Not available in some countries; not available to some institutions; not available for some uses.