Ponatinib AP24534 cas 943319-70-8

Ponatinib is a potent, orally available multi-targeted kinase inhibitor with IC₅₀ of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.Ponatinib (AP24534) potently inhibits native ABL (IC₅₀: 0.37 nM), ABL^T315I (IC₅₀: 2.0 nM), and other clinically important ABL kinase domain mutants (IC₅₀: 0.30-0.44 nM). Ponatinib also inhibits SRC (IC₅₀: 5.4 nM) and members of the VEGFR, FGFR, and PDGFR families of receptor tyrosine kinases. Ponatinib potently inhibits proliferation of Ba/F3 cells expressing native BCR-ABL (IC₅₀: 0.5 nM). All BCR-ABL mutants tested remained sensitive to Ponatinib (IC₅₀: 0.5-36 nM) including BCR-ABL^T315I (IC₅₀: 11 nM). Ponatinib (AP24534) inhibits the in vitro kinase activity of FLT3, KIT, FGFR1, and PDGFRα with IC₅₀ values of 13, 13, 2, and 1 nM, respectively. Ponatinib inhibits phosphorylation of all 4 RTKs in a dose-dependent manner, with IC₅₀ values between 0.3 to 20 nM. Consistent with these activated receptors being important in driving leukemogenesis Ponatinib also potently inhibits the viability of all 4 cell lines with IC₅₀ values of 0.5 to 17 nM. In contrast, the IC₅₀ for inhibition of RS4;11 cells which express native (unmutated) FLT3, is more than 100 nM.

Related Prodcuts:

Sorafenib; Sunitinib malate; Cabozantinib; Cabozantinib malate; Axitinib; Vandetanib; Nintedanib; Regorafenib; Pazopanib HCl; Pazopanib; Cediranib; Dovitinib; Lenvatinib; Tivozanib; Sorafenib Tosylate

[1]. 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, 2009, 16(5), 401-412.

[2]. Gozgit JM, et al. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther, 2011, 10(6), 1028-1035.

[3]. Uchida T, et al. Hes1 upregulation contributes to the development of FIP1L1-PDGRA-positive leukemia in blast crisis. Exp Hematol. 2014 May;42(5):369-379.e3.