ELIMUSERTIB

Potency assay (off target): BAY 1895344 was evaluated in an in-house kinase selectivity panel, as well as by KINOMEscan profiling performed by DiscoverX, revealing a promising kinase selectivity profile. Of the 31 kinases in the in-house panel, only the IC50 value from the biochemical mTOR assay (IC50: 35 nM) was of the same order of magnitude as for ATR. In the KINOMEscan panel, 1 μM BAY 1895344 exhibited activity against only six of a total of 468 kinases: for only three of these kinases Kd values below 1 μM were recorded [mTOR, cyclin G-associated kinase (GAK), and right open reading frame kinase 2 (RIOK2); Kd = 24, 580, and 660 nM, respectively].

Potency assay, off target (cells): BAY 1895344 showed good selectivity against mTOR (ratio of IC50 values: mTOR/ATR 61) in cellular mechanistic assays. Moreover, BAY 1895344 revealed high selectivity against other related kinases, such as DNA-PK (IC50: 332 nM), ATM (IC50: 1420 nM), and PI3Kβ (IC50: 3270 nM).