| Description | AZD-8835 is a mixed inhibitor of PI3Kα/δ (IC50: 6.2/5.7 nM), also with selectivity against PI3Kβ/γ (IC50: 431/90 nM). |
| In vitro | AZD8835是一种对PI3Kα（野生型、E545K和H1047R突变）和PI3Kδ具有强效抑制作用的化合物，相对于PI3Kβ和PI3Kγ展现出极佳的选择性，并且具有极佳的一般激酶选择性。在对PI3Kα抑制敏感的细胞中（PIK3CA突变的人乳腺导管癌BT474细胞系中的IC50=0.057 μM），以及对PI3Kδ抑制敏感的细胞中（JeKo-1 B细胞系的IC50=0.049 μM），AZD8835能强效地抑制p-Akt；然而，对于对PI3Kβ抑制敏感的细胞（PTEN缺失的乳腺腺癌MDA-MB-468细胞系的IC50=3.5 μM）或对PI3Kγ抑制敏感的细胞（单核细胞RAW264细胞系的IC50=0.53 μM）则不是如此。 |
| In vivo | AZD8835 在连续给药的情况下对应的乳腺癌异种移植模型显示出抗肿瘤效能，并且具有高代谢稳定性和适合口服给药的物理特性[1][2]。 |
| Cell experiments | BT474, MCF7, or T47D cells are seeded in 384-well plates at a density of 500 to 2,000 cells per well and incubated overnight. Cells are dosed with compound(s) and cell confluency is measured at 4-hour intervals over several days.(Only for Reference) |
| Target activity | PI3Kα:6.2 nM, PI3Kδ:5.7 nM |
| Synonyms | AZD8835 |
| molecular weight | 469.54 |
| Molecular formula | C22H31N9O3 |
| CAS | 1620576-64-8 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: < 1 mg/mL (insoluble or slightly soluble) DMSO: 86 mg/mL (183.2 mM) |
| References | 1. Hudson K, et al. Mol Cancer Ther. 2016, 15(5):877-89. 2. Bernard Barlaam, et al. Bioorganic & Medicinal Chemistry Letters. 2015, 25(22):5155-5162. |