JNJ-47117096 is a potent and selective MELK inhibitor with an IC50 of 23 nM, and it also exhibits strong activity against Flt3 with an IC50 of 18 nM.

JNJ-47117096 is a potent and selective inhibitor of MELK, with an IC50 of 23 nM. It also effectively inhibits Flt3 with an IC50 of 18 nM, and weakly blocks CAMKIIδ, Mnk2, CAMKIIγ, and MLCK, with IC50 values of 810 nM, 760 nM, 1000 nM, and 1000 nM, respectively. JNJ-47117096 (MELK-T1) suppresses the proliferation of Flt3-driven Ba/F3 cell lines in the absence of IL-3, with an IC50 of 1.5 μM, but shows no inhibitory activity in the presence of IL-3. It does not inhibit the proliferation of Ba/F3 cell lines transfected with FGFR1, FGFR3, or KDR, regardless of IL-3 presence [1]. At a concentration of 10 μM, JNJ-47117096 delays the entry of MCF-7 cells into the S phase. By inhibiting MELK, JNJ-47117096 causes replication fork stalling and DNA double-strand breaks (DSB) and activates the ATM-mediated DNA damage response (DDR). At concentrations of 3 and 10 μM, it induces growth arrest and a senescent phenotype while strongly phosphorylating p53, upregulating p21 over the long term, and downregulating FOXM1 target genes [2].