BAY-1125976 is an allosteric inhibitor of Akt1 and -2 (IC50s = 5.2 and 18 nM, respectively, in a time-resolved FRET assay). It is selective for Akt1 and -2 over Akt3 (IC50 = 427 nM in the same assay) but does inhibit the activity of the receptor tyrosine kinases FLT1, -3, -4, and Mer by greater than 50% in a panel of 227 kinases at 1 μM. BAY-1125976 inhibits the proliferation of 23 cancer cell lines (IC50s = 0.02-10 μM) and reduces tumor growth in KPL-4, MCF-7, and patient-derived xenograft (PDX) mouse models when administered at a dose of 50 mg/kg per day.
