Radotinib-d6 (Synonyms: IY-5511)

Radotinib-d₆ is intended for use as an internal standard for the quantification of radotinib by GC- or LC-MS. Radotinib is a second generation tyrosine kinase inhibitor that targets both the wild-type and mutant forms of Bcr-Abl (IC₅₀ = 30.6 nM in Ba/F3 human chronic myeloid leukemia cells expressing the wild-type enzyme).¹ Radotinib also inhibits platelet-derived growth factor receptors (PDGFRs) α and β with IC₅₀ values of 75.5 and 130 nM, respectively.^2,3 Binding of radotinib to Bcr-Abl in vitro inhibits the phosphorylation of the downstream signaling mediator CrkL.³ In acute myeloid leukemia cells, in vitro treatment with radotinib at doses of 10 to 100 µM reduces viability, activates the mitochondrial apoptosis pathway, and promotes expression of the differentiation marker CD11b.²

1.Zabriskie, M.S., Vellore, N.A., Gantz, K.C., et al.Radotinib is an effective inhibitor of native and kinase domain-mutant BCR-ABL1Leukemia29(9)1939-1942(2015) 2.Heo, S.-K., Noh, E.-K., Yoon, D.-J., et al.Radotinib induces apoptosis of CD11b+ cells differentiated from acute myeloid leukemia cellsPLoS One10(6)e0129853(2015) 3.Kim, S.-H., Menon, H., Jootar, S., et al.Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitorsHaematologica99(7)1191-1196(2014)