AZD-8835

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

AZD-8835  纯度: 98.63%

AZD8835 是一种有效的选择性 PI3KαPI3Kδ 抑制剂,IC50 分别为 6.2 和 5.7 nM。

AZD-8835

AZD-8835 Chemical Structure

CAS No. : 1620576-64-8

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10 mM * 1 mL in DMSO ¥1033 In-stock
5 mg ¥1000 In-stock
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生物活性

AZD8835 is a potent and selective inhibitor of PI3Kα and PI3Kδ with IC50s of 6.2 and 5.7 nM, respectively.

IC50 & Target[1]

PI3Kδ

5.7 nM (IC50)

PI3Kα

6.2 nM (IC50)

PI3Kα-H1047R

5.8 nM (IC50)

PI3Kα-E545K

6 nM (IC50)

PI3Kγ

90 nM (IC50)

PI3Kβ

431 nM (IC50)

体外研究
(In Vitro)

The selectivity profile of AZD8835 (Compound 25) among the class I PI3K isoforms is tested in enzyme and cell based assays. At the enzyme level, AZD8835 is a potent mixed inhibitor of PI3Kα (IC50 6.2 nM) and PI3Kδ (IC50 5.7 nM), with selectivity against PI3Kβ (IC50 431 nM) and PI3Kγ (IC50 90 nM). AZD8835 is also a potent inhibitor of the commonly occurring PI3Kα mutants, PI3Kα- E545K (IC50 6 nM) and PI3Kα-H1047R (IC50 5.8 nM). In cell-based assays assessing the ability to inhibit Akt phosphorylation, AZD8835 is a potent inhibitor in cells sensitive to PI3Kα inhibition (IC50 57 nM in PIK3CA mutant human breast ductal carcinoma BT474 cell line) and in cells sensitive to PI3Kδ inhibition (IC50 49 nM in Jeko-1 B cell line, but not to cells sensitive to PI3Kβ inhibition (IC50 3.5 μM in PTEN null breast adenocarcinoma MDA-MB-468 cells) or to PI3Kγ inhibition (IC50 530 nM in monocytic RAW264 cell line)[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.

体内研究
(In Vivo)

AZD8835 (Compound 25) displays good solubility, good permeability and low turnover in hepatocytes from various species. As expected from the in vitro data, low in vivo clearance associated with high bioavailability is seen in both rat and dog. AZD8835 shows high exposure following oral administration to SCID mice (AUC: 137 μM.h and Cmax 34 μM at 50 mg/kg p.o.) and is selected for further in vivo evaluation. In a pharmacodynamic experiment following chronic oral dosing (25 mg/kg b.i.d. or 6 mg/kg b.i.d. of AZD8835) in nude mice bearing mutant H1047R PI3Kα SKOV-3 tumour xenografts, target modulation is assessed by measuring Akt phosphorylation levels at Ser473 at 30 minutes and 8 hours. At both doses, strong inhibition of Akt phosphorylation is observed at the 30 minute timepoint. At 8 hours, significant inhibition is still seen at the 25 mg/kg dose, whereas no inhibition is seen at the lower dose of 6 mg/kg, consistent with the lower plasma concentrations observed[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.

Clinical Trial

分子量

469.54

Formula

C22H31N9O3

CAS 号

1620576-64-8

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 20 mg/mL (42.59 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1297 mL 10.6487 mL 21.2974 mL
5 mM 0.4259 mL 2.1297 mL 4.2595 mL
10 mM 0.2130 mL 1.0649 mL 2.1297 mL

*

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。

In Vivo:

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 mg/mL (4.26 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.26 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.0 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

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2 mg/mL (4.26 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.26 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2 mg/mL (4.26 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.26 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Barlaam B, Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5155-62.

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