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Novel bis-(1H-indol-2-yl)-methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase

Mahboobi, Siavosh ; Uecker, A. ; Sellmer, A. ; Cénac, C. ; Höcher, H. ; Pongratz, H. ; Hufsky, H. ; Trümpler, A. ; Sicker, M. ; Heidel, F. ; Fischer, T. ; Stocking, C. ; Elz, Sigurd ; Böhmer, F.-D. ; Dove, Stefan



Abstract

FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivs. were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors I and II show IC50 values of 0.06 and ...

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