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. 2020 Feb 26;19(5):884–899. doi: 10.1074/mcp.RA119.001504

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© 2020 van Alphen et al.

Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.

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Fig. 4. — Validation of potential kinase drivers in four AML cell lines without identified driver mutations. A, INKA score ranking for the MM6 and Kasumi-3 cell lines indicates high activity of the FLT3 and PDGFRA kinases while ranking in KG-1 and KG-1a cell lines uncovers FGFR1 (arrows). B, List of experimentally established drug targets of ponatinib (green panel), quizartinib (pink panel) and ibrutinib (blue panel) with an affinity below 500 nm. Targets indicated by circles were discovered through a chemical proteomics approach (40), and those indicated by triangles used cell-free essays for target identification (39, 43, 72). Bold font indicates kinases that are intended targets of the drug, whereas plain font indicates additional target kinases. Kinases with a top 20 INKA score in the KG-1, KG-1a, MM-6 and Kasumi-3 cell lines are indicated with the corresponding colors as in panel A. C, Targeting of suspected driver kinases in the above cell lines with a KI effective against FGFR1 (ponatinib), or FLT3 and PDGFRA (quizartinib) shows effective inhibition of cell viability in the nanomolar range. Ibrutinib is used as a control.