• June 15, 2021

Ponatinib, free base

Description

  • Ponatinib, also known as AP24534, is a multi-target tyrosine kinase inhibitor and is active against T315I and other BCR-ABL mutants. Ponatinib inhibited native BCR-ABL (IC50 = 0.37 nM) and mutants with IC50 values ​​of 2 nM (T315I); 0.44 nM (Q252H); 0.3 nM (Y253F); 0.3 nM (M351T); and 0.34 nM (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 on 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 viability and FGFR-mediated signaling 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 deregulated FGFRs. Ponatinib treatment reduced tumor growth and inhibited signaling in all three mouse tumor models examined. Go get, J.M. et al. “Ponatinib (AP24534), a multi-targeted 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 previously treated 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 Minutes (Post-Meeting Edition) 30: 6503 (2012).
  • Ponatinib is the active ingredient in the drug that is sold under the trade name Iclusig®. This drug is currently approved in at least one country for use in patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. NOTE: THE PONATINIB SOLD BY LC LABORATORIES FOR RESEARCH IS NOT ICLUSIG® AND IS NOT FOR HUMAN USE.
  • Related CAS numbers: 1114544-31-8 for ponatinib HCl salt.
  • Another CAS number previously assigned to Ponatinib, Free Base, namely 952306-26-2, has been removed 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 USA; (ii) Section 69.1 of the Patent Law of Japan in Japan; (iii) Section 11, No. 2 of the German Patent Law 1981; (iv) Section 60, Paragraph 5b of the United Kingdom Patents Act 1977 in the United Kingdom; (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 along with its amendment by the Statutes Amendment Bill of 2002; (vii) the legislation and/or related jurisprudence that may be or become applicable in the aforementioned countries; and (viii) similar laws and rules that may apply in various other countries.
  • Not available in some countries; not available for some institutions; not available for some uses.

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