BAY-1125976.

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.

BAY1125976 is a selective allosteric Akt1/Akt2 inhibitor; inhibits Akt1 and Akt2 activity with IC50 values of 5.2 nM and 18 nM at 10 μM ATP, respectively.

Akt1: 5.2 nM (IC₅₀, at 10 μM ATP); Akt2: 18 nM (IC₅₀, at 10 μM ATP); Akt3: 427 nM (IC₅₀, at 10 μM ATP)

[1] Politz O, et al. BAY 1125976, a selective allosteric AKT1/2 inhibitor, exhibits high efficacy on AKT signaling-dependent tumor growth in mouse models. Int J Cancer. 2017 Jan 15;140(2):449-459. DOI:10.1002/ijc.30457