Iclusig – pro
Ponatinib (Iclusig, AP24534) was FDA approved for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). It was approved based on the inital results of The PACE (Ponatinb Ph+ ALL and CML Evaluation) trial and has activity against the T315I mutation, which confers resistant to other CML drugs. It targets the Bcr-Abl tyrosine kinase, as well as VEGFR, PDGFR, FGFR, the SRC kinases, KIT, EPH receptors, RET, TIE2, and FLT3. The multi-targeting makes it an attractive candidate for personalized use for conditions that display these mutations in the Personalized Medicine approach.
Singh et al, Molecular Monitoring and Treatment of Chronic Myeloid Leukemia (CML) J Clin Exp Pathol 2012, 2:4
Huang, WS; Metcalf, CA; Sundaramoorthi, R; Wang, Y; Zou, D; Thomas, RM; Zhu, X; Cai, L et al. (2010). “Discovery of 3-2-(imidazo1,2-bpyridazin-3-yl)ethynyl-4-methyl-N-{4-(4-methylpiperazin-1-yl)methyl-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant”. Journal of Medical Chemistry 53 (12): 4701–19.
O’Hare, T; Shakespeare, WC; Zhu, X; Eide, CA; Rivera, VM; Wang, F; Adrian, LT; Zhou, T 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 (5): 401–12.
Khodadoust MS, Luo B, Medeiros BC, et al. Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia. 2016;30(4):947‐950. doi:10.1038/leu.2015.136
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