BAY1125976 (C09-0785-873)

InformationBAY 1125976 is a selective allostericAKT1/2inhibitor,exhibits high efficacy on AKT signaling-dependent tumor growth in mouse models. BAY1125976 inhibits the activity ofAKT1(IC50 = 5.2 nM at 10 µM ATP and 44 nM at 2 mM ATP) andAKT2(IC50 = 18 nM at 10 µM ATP and 36 nM at 2 mM ATP) very potently.Whereas BAY1125976 is almost inactive onAKT3(IC50 = 427 nM at 10 µM ATP).TargetsAkt1 (at 10 µM ATP); Akt2 (at 10 µM ATP); Akt2 (at 2 mM ATP); Akt1 (at 2 mM ATP); Akt3 (at 10 µM ATP) 5.2 nM; 18 nM; 36 nM; 44 nM; 427 nMIn vitroBAY 1125976 inhibits activation of AKT in cell lines carrying the AKT-activating mutation E17K. In KU-19-19 bladder cancer cells activation by phosphorylation is inhibited at AKT1-S473 and 4EBPI-T70 with IC50 values of 35 and 100 nM, respectively. In the prostate cancer cell line LAPC-4, the phosphorylation of AKT1-S473, T308 and 4EBP1-T70 is inhibited with IC50 values of 0.8, 5.6 and 35 nM, respectively. Treatment of LAPC-4 cells with BAY 1125976 results in an inhibition of PRAS40 phosphorylation at T246 as a direct target of AKT1 activity with an IC50 of ∼141 nM. BAY 1125976 inhibits the proliferation of the breast cancer cell lines BT-474, T47D, MCF7, ZR-75–1, EVSA-T, MDA-MB-453, KPL-4 and BT20 as well as the prostate cancer cell lines LNCaP and LAPC-4 with submicromolar IC50 values. Breast cancer cell lines of luminal type show strong inhibition of cell proliferation following BAY 1125976 treatment..In vivoTreatment with different doses of BAY 1125976 results in potent antitumor efficacy in KPL-4 tumor bearing mice. A clear, statistically significant dose-response is observed after daily oral treatment with 25 or 50 mg/kg BAY 1125976 with T/Cvolume ratios of 0.14 and 0.08, respectively. Daily administration of 25 or 50 mg/kg BAY 1125976 results in significant antitumor efficacy in MCF7-implanted nude mice compared with the control with T/Cvolume values of 0.25 and 0.25 and T/Cweight values of 0.33 and 0.37, respectively. BAY 1125976 displays good antitumor efficacy in vivo in AKT1E17K mutated models..Cell Research(from reference)Cell lines：13 human breast cancer cell lines and 10 other cancer cell lines. Specification: 0.98 Molecular Formula: C23H21N5O Molecular Weight: 383.45 PubChem CID: 70817911 Isomeric SMILES: C1CC(C1)(C2=CC=C(C=C2)C3=C(N4C(=N3)C=CC(=N4)C(=O)N)C5=CC=CC=C5)N Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/B414031-SCI_f3c793551aaea36953fbf50380030327.pdf