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A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia

Sellmer, Andreas ; Pilsl, Bernadette ; Beyer, Mandy ; Pongratz, Herwig ; Wirth, Lukas ; Elz, Sigurd ; Dove, Stefan ; Henninger, Sven Julian ; Spiekermann, Karsten ; Polzer, Harald ; Klaeger, Susan ; Kuster, Bernhard ; Böhmer, Frank D. ; Fiebig, Heinz-Herbert ; Krämer, Oliver H. ; Mahboobi, Siavosh


Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the ...


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