MK-8745

We demonstrated that using HTS can considerably shorten drug discovery time scales, leading to the identification of promising lead compounds. Our study is the first to provide preclinical evidence of the antileukemic activity of AURKAi, with particular focus on NPM1-mutated AML.

In the validation assay, 2 compounds (MK-5108 and MK-8745) were confi rmed as more active against NPM1-mutated than NPM1–wild-type AML cells by either CyQUANT or apoptosis assay. Strikingly, we confi rmed selectivity for two additional AURKAi (Alisertib and ENMD-2076, both isoform-selective inhibitors of AURKA) that were not included in the screening library... We demonstrated that using HTS can considerably shorten drug discovery time scales, leading to the identifi cation of promising lead compounds. Our study is the fi rst to provide preclinical evidence of the antileukemic activity of AURKAi, with particular focus on NPM1-mutated AML.

However, the presence of necroptosis was ruled out in MK-5108-treated IMR-32 and CHP-134 cells. In summary, the effects of the combination of ch14.18/CHO mAb and aurora A kinase inhibitors (MK-5108 and MK-8745) were shown to enhance apoptosis in IMR-32 cells compared to when used individually.