BAY-885 shows potent ERK5 kinase and transcriptional inhibition in the SN12C-MEF2 reporter cell line (IC50 = 115 nM/IC90 = 691 nM) and has no effects on a reporter control cell line with constitutive luciferase expression (SN12C-CMV-luc, IC50 > 30 μM), thereby ruling out potential effects as a general inhibitor of transcription or translation.
BAY-885 is an ATP site-targeting, potent and selective ERK5 (BMK1, MAPK7) inhibitor (IC50 = 35 nM with 250 μM ATP; % inhibition at 1 μM = 62/r at Fer, 58/human EphB3, 43/human EphA5, =20/355 kinases) with no BRD4 affinity (20 μM), nor inhibitory potency toward hERG (10 μM) and CYP enzymes (20 μM; CYP1A2, CYP2C8, CYP2C9, CYP2D6, CYP3A4). BAY-885 potently inhibits 100 ng/mL EGF-induced, ERK5-dependent MEF2 activity (IC50 = 120 nM; SN12C-MEF2-luc reporter assay).
