Bosutinib | Dual Src/Abl kinase inhibitor

Bosutinib (380843-75-4) is an ATP-competitive dual Src/Abl kinase inhibitor (IC₅₀ = 1 nM).¹  It potently inhibits the apoptosis-linked STE20 kinases but does not inhibit Kit or PDGFR.² Bosutinib was found to inhibit 16 of 18 imatinib-resistant mutant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutants.³ Enhances retinoic acid-induced differentiation of HL-60 leukemia cells.⁴ Suppresses migration and invasion of human breast cancer cells (IC₅₀ = 250 nM which is also the IC₅₀ for inhibition of cellular Src kinase activity in intact tumor cells).⁵

References/Citations:

1. Golas et al. (2003), SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice; Cancer Res., 63 375
2. Remsing Rix et al. (2009), Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells; Leukemia, 23 477
3. Redaelli et al. (2009), Activity of bosutinib, Dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants; J. Clin. Oncol., 27 469
4. MacDonald et al. (2018), Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells; Leuk. Lymphoma, 59 2941
5. Vultur et al. (2008), SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells; Mol. Cancer Ther., 7 1185