AZD5363
(Synonyms: 4-氨基-N-[(1S)-1-(4-氯苯基)-3-羟基丙基]-1-(7H-吡咯并[2,3-D]嘧啶-4-基)-4-哌啶甲酰胺,AZD5363) 目录号 : GC11752
A pan-Akt inhibitor
Cas No.:1143532-39-1
Sample solution is provided at 25 µL, 10mM.
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AZD5363 is a novel, potent phosphoinositide 3-kinase (PI3K)/Akt pathway inhibitor with IC50 value of ~200nM. [1]
AZD5363 is proved to inhibit castrate resistant prostate cancer (CRPC) progression. Clusterin (CLU) and autophagy will be induced which may work as cytoprotective responses which can affect the downstream PI3K/Akt signaling. [2] AZD5363 inhibits the growth of a lot of human tumor cells in a dose dependent manner. The mode of action could be monotherapy as well as in combination with HER2 inhibitors in breast cancer models. [3] It is suggested to induce cell apoptosis by measuring the expression of PARP cleavage, the activity of Caspase 3, et al. [1]
Most importantly, AZD5363 can target the PI3K/Akt-pathway in vivo significantly, thus reducing the serum PSA-levels and tumor volume, finally, it could postpone the progression to CRPC.[1]
References:
[1] Thomas C, Crafter C, Davies B, Zoubeidi A, Gleave ME. AZD5363, A novel AKT inhibitor, delays prostate cancer progression. The Journal of Urology. May 2011. 185(4S): e292-293.
[2] Kumano M, Zhang F, Shiota M, Crafter C, Davies B, Zoubeidi A, Gleave M. Clusterin knockdown enhances antitumor activity of a novel Akt inhibitor, AZD5363, through inhibition of autophagy in prostate cancer. The Journal of Urology. May 21 2012. e392.
[3] Davies BR, Greenwood H, Dudley P, et al. Preclinical Pharmacology of AZD5363, an Inhibitor of AKT: Pharmacodynamics, Antitumor Activity, and Correlation of Monotherapy Activity with Genetic Background. Mol. Cancer Ther. Arp 2012. 11: 873.
| Cell experiment: [1] | |
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Cell lines |
GSK3 in BT474c (Her2þ PIK3CAmutant breast), LNCaP (PTEN-null prostate) and MDA-MB-468 (PTEN-null breast) cancer cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
pGSK3β (IC50: 0.76 μM in BT474c, 0.06 μM in LNCaP, 0.38 μM in MDA-MB-468) pPRAS40 (IC50: 0.31 μM in BT474c, 0.22 μM in LNCaP, 0.39 μM in MDA-MB-468) pFOXO3a translocation (IC50: 0.69 μM in BT474c) |
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Applications |
AZD5363 inhibited phosphorylation of AKT substrates with IC50 values of 0.06 to 0.76 μM in the 3 cell lines. AZD5363 also effectively inhibited phosphorylation of S6 and 4E-BP1 in BT474c cells and LNCaP cells. |
| Animal experiment : [1] | |
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Animal models |
Nude mice bearing BT474c xenografts |
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Dosage form |
The treatment groups received 300 or 100 mg/kg acute dose of AZD5363 solubilized in a DMSO/Kleptose buffer, by oral gavage. |
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Applications |
Oral dosing of AZD5363 to nude mice caused dose and time-dependent reduction of PRAS40, GSK3, and S6 phosphorylation. Following a 300 mg/kg dose of AZD 5363, phosphorylation of all 3 biomarkers was significantly inhibited for at least 24 hours. 100 mg/kg dose of AZD5363 significantly inhibited phosphorylation of the 3 biomarkers was for at least 8 hours. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Davies B R, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Molecular cancer therapeutics, 2012, 11(4): 873-887. |
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| Cas No. | 1143532-39-1 | SDF | |
| 别名 | 4-氨基-N-[(1S)-1-(4-氯苯基)-3-羟基丙基]-1-(7H-吡咯并[2,3-D]嘧啶-4-基)-4-哌啶甲酰胺,AZD5363 | ||
| 化学名 | 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide | ||
| Canonical SMILES | C1CN(CCC1(C(=O)NC(CCO)C2=CC=C(C=C2)Cl)N)C3=NC=NC4=C3C=CN4 | ||
| 分子式 | C21H25ClN6O2 | 分子量 | 428.92 |
| 溶解度 | ≥ 21.45mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3314 mL | 11.6572 mL | 23.3144 mL |
| 5 mM | 0.4663 mL | 2.3314 mL | 4.6629 mL |
| 10 mM | 0.2331 mL | 1.1657 mL | 2.3314 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet