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.

BAY 1125976 is equally potent against Akt1 (IC₅₀=5.2 nM at 10 μM ATP and 44 nM at 2 mM ATP) and Akt2 (IC₅₀=18 nM at 10 μM ATP and 36 nM at 2 mM ATP) isoforms and up to 86 fold less potent against Akt3 (IC₅₀=427 nM at 10 μM ATP). It inhibits the Akt1 and Akt2 by binding into an allosteric binding pocket formed by kinase and PH domain. It inhibits cell proliferation in a broad panel of human cancer cell lines, particularly in breast and prostate cancer cell lines expressing estrogen or androgen receptors. It effectively blocks Akt signaling by inhibiting the phosphorylation of Akt and the downstream effectors, including eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), glycogen synthase kinase 3 beta (GSK3s), proline-rich Akt substrate 40 kDa (PRAS40), S6 ribosomal protein (S6RP), and 70 kDa ribosomal protein S6 kinase 1 (70S6K)^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

BAY 1125976 targets tumors displaying activation of the PI3K/Akt/mTOR pathway. BAY 1125976 exhibits strong in vivo efficacy in both cell line and patient-derived xenograft models such as the KPL4 breast cancer model (PIK3CA^H1074R mutant), the MCF7 and HBCx-2 breast cancer models, and the Akt^E17K mutant driven prostate cancer (LAPC-4) and anal cancer (AXF 984) models^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

383.45

C₂₃H₂₁N₅O

1402608-02-9

Room temperature in continental US; may vary elsewhere.

DMSO : 25 mg/mL (65.20 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (6.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.52 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [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.

PEG/water (60/40), pH 4.0, is used as a vehicle for BAY 1125976. The selectivity of BAY 1125976 is assessed using two different kinase panels: the 230 kinase panel; and the 468 kinase panel. In the 230 kinase panel, kinase activity is determined after incubation with 10 μM BAY 1125976. An additional incubation with 1 μM and 0.1 μM BAY 1125976 is performed for the kinases where 10 μM BAY 1125976 shows an inhibition over 70%. All tests are performed at 10 μM ATP. The 468-kinase panel covered AGC, CAMK, CMGC, CK1, STE, TK, TKL, lipid, and atypical kinase families. The profiling is performed by combining the test compound with DNA-tagged kinase and immobilized ligands. The final kinase concentrations are measured by quantitative PCR^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice: Female NMRI (nu/nu) mice s.c. injected with 3 x 10⁶/100 μL KPL-4 breast cancer cells are used to study the mode-of-action of BAY 1125976. The treatment is started when tumors reaches 232-358 mm³ in size and the mice receive a single oral dose of 25 or 50 mg/kg BAY 1125976. For determination of plasma concentration-time profiles, blood is drawn from the animals at different time points after compound administration^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.