JNJ-47117096 hydrochloride is a potent and selective MELK inhibitor with an IC50 of 23 nM and also effectively inhibits Flt3 with an IC50 of 18 nM.

MELK:23 nM , FLT3:18 nM

JNJ-47117096 demonstrates selectivity in its mechanism, showing no inhibitory effects on Ba/F3 cell proliferation transfected with FGFR1, FGFR3, or KDR, irrespective of IL-3 presence. At a concentration of 10 μM (MELK-T1), it notably slows MCF-7 cell progression through S-phase and targets MELK to induce replication forks stalling and DNA double-strand breaks (DSBs), subsequently activating the ATM-mediated DNA damage response (DDR). Furthermore, at 3 and 10 μM, it initiates growth arrest and a senescence phenotype, significantly increasing p53 phosphorylation, sustained p21 up-regulation, and down-regulation of FOXM1 target genes. As a MELK inhibitor, JNJ-47117096 hydrochloride exhibits potent and selective inhibition with an IC50 of 23 nM, also effectively inhibiting Flt3 (IC50 of 18 nM) and moderately affecting CAMKIIδ, Mnk2, CAMKIIγ, and MLCK (IC50s: 810 nM, 760 nM, 1000 nM, 1000 nM). Specifically, JNJ-47117096 (MELK-T1) suppresses Flt3-driven Ba/F3 cell line proliferation with an IC50 of 1.5 μM in the absence of IL-3, showing no inhibitory activity when IL-3 is present.