AZD5363 |
Catalog No.GC11752 |
AZD5363(AZD5363)은 Akt1, Akt2 및 Akt3에 대해 IC50이 각각 3, 7 및 7 nM인 경구 활성 및 강력한 범-AKT 키나제 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1143532-39-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: [1] | |
Cell lines |
GSK3 in BT474c (Her2þ PIK3CAmutant breast), LNCaP (PTEN-null prostate) and MDA-MB-468 (PTEN-null breast) cancer cells |
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. |
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) |
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] | |
Animal models |
Nude mice bearing BT474c xenografts |
Dosage form |
The treatment groups received 300 or 100 mg/kg acute dose of AZD5363 solubilized in a DMSO/Kleptose buffer, by oral gavage. |
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. |
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. |
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. |
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.
Cas No. | 1143532-39-1 | SDF | |
Chemical Name | 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 | ||
Formula | C21H25ClN6O2 | M.Wt | 428.92 |
Solubility | ≥ 21.45mg/mL in DMSO | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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