MELK-8a hydrochloride is a potent inhibitor of maternal embryonic leucine zipper kinase (MELK, IC50 = 2 nM). 

MELK:2 nM

MELK-8a hydrochloride inhibits the growth of MDA-MB-468 cells and MCF-7 cells with an IC50 of approximately 0.06 and 1.2 μM, respectively. MELK-8a hydrochloride remains very potent with an IC50 of 140 nM when the ATP concentration in the biochemical assay is shifted from 20 μM to 2 mM. MELK-8a hydrochloride only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1 μM demonstrating great selectivity. MELK-8a hydrochloride is at least 90-fold more selective in targeting MELK in all cases. MELK-8a hydrochloride is fairly soluble (0.22 g/L at pH 6.8) and shows a good permeability in the Caco-2 assay[1].

In C57BL/6 mice, MELK-8a hydrochloride (30 mg/kg; s.c.) results in good plasma exposure. The compound adsorption into the systemic circulation is rapid (Tmax=0.4 h) and peak plasma concentration reaches 6.6 μM. An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120 mg/kg and all clearance mechanisms can be saturated at 240 mg/kg. However, MELK-8a hydrochloride (10 mg/kg; oral) shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance[1].