| Description | AZD8186 is an effective and specific PI3Kβ/δ inhibitor (IC50: 4/12 nM). |
| In vitro | AZD8186 强效抑制对PI3Kβ抑制敏感的MDA-MB-468细胞中的p-Akt以及对PI3Kδ抑制敏感的Jeko B细胞，其IC50分别为3 nM和4 nM。[1] 在大多数PTEN缺失的细胞系中，AZD8186 显示出优先的生长抑制活性，其GI50为<1 μM。[2] |
| In vivo | 在裸鼠体内携带PTEN缺失的PC3前列腺肿瘤异种移植物模型中，AZD8186（100 mg/kg，口服）显著抑制Akt磷酸化水平，并且显著抑制肿瘤生长。当与ABT联合使用时，AZD8186（60 mg/kg，口服）能够完全抑制肿瘤生长。[1] 在小鼠PTEN-null TNBC模型HCC70和MDA-MB-468，以及前列腺模型HID28中，AZD8186（50 mg/kg，口服）也能抑制肿瘤生长。[2] 使用AZD8186与雄激素剥夺疗法的联合治疗可导致持久的肿瘤退缩，且该效果在治疗停止后仍然持续。[3] |
| Cell experiments | Cells are seeded in 96-well plates, at a density to allow for logarithmic growth during the 72 hour assay, and incubated overnight at 37°C, 5% CO2. Cells are treated with AZD8186 (30 to 0.003 μM) for 72 hours and cell proliferation measured by MTS. The CellTiter Aqueous Non-Radioactive Cell Proliferation Assay reagent is used in accordance with the manufacturer's protocol and Absorbance measured with Tecan Ultra instrument. Pre-dose measurements are made and the concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) values are determined.(Only for Reference) |
| Target activity | PI3Kδ:12 nM, PI3Kβ:4 nM |
| molecular weight | 457.47 |
| Molecular formula | C24H25F2N3O4 |
| CAS | 1627494-13-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 3 mg/mL (6.6 mM) DMSO: 84 mg/mL (183.6 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) |
| References | 1. Barlaam B, et al. J Med Chem. 2015, 58(2), 943-962. 2. Hancox U, et al. Mol Cancer Ther. 2015, 14(1), 48-58. 3. Marques RB, et al. Eur Urol. 2015, 67(6), 1177-1185. |