Kinase inhibitor (including Pan-Bcr-Abl). Suppresses cytokine storm in mouse models; Inhibits SARS-CoV-2 in cells. Gordon et al. bioRxiv, Mar 23 2020, https://doi.org/10.1101/2020.03.22.002386; Gordon et al. Nature, Apr 30 2020, https://doi.org/10.1038/s41586-020-2286-9.
Biochemicals & reagents
1) O’Hare et al. (2009), AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance; Cancer Cell, 16 401 2) Gozgit et al. (2011), Potent activity of ponatinib (AP24535) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies; Mol. Cancer Ther., 10 1028 3) Gozgit et al. (2012), Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models; Mol. Cance Ther., 11 690 4) Chen et al. (2019), Ponatinib Protects Mice From Lethal Influenza Infection by Supressing Cytokine Storm; Front. Immunol., 10 1393
Ponatinib is a highly potent pan-Bcr-Abl and multikinase inhibitor, suppressing the activity of native Bcr-Abl (IC50=0.37 nM) as well as the mutants T315I (IC50=2 nM), Q252H (IC50=0.44 nM), Y253F (IC50=0.3 nM), M351T (IC50=0.3 nM) and H396P (IC50=0.34 nM) (1). This compound also inhibits PDGFRα, c-Src and c-Kit (IC50=1.1, 5.4 and 12.5 nM respectively) (2), as well as FGFR-mediated signaling (IC50<40 nM) (3). It also protects against influenza A virus-induced death by suppressing cytokine storm in mouse models (4).