A-674563 |
| Catalog No.GC11875 |
A-674563 est un inhibiteur d'Akt1 actif et sélectif par voie orale avec un Ki de 11 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 552325-73-2
Sample solution is provided at 25 µL, 10mM.
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A-674563 is a potent and selective Akt1 inhibitor with IC50 value of 14 nM. A-67453 also inhibited PKA and Cdk2 with IC50 value of 16 nM and 46 nM.
Akt, also known as protein kinase B, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.
In MiaPaCa-2 cells treated with A-674563 for 48 hour, it slowed the tumor cell proliferation (EC50 = 0.4 μm). In STS cells, phosphorylation of GSK3 and MDM2 was prominently reduced by A-674563 treatment. [1] Akt inhibition-induced G2 cells cycle arrest and apoptosis were also observed in A563-treated STS cells. [2]
In scid mice carrying established PC-3 tumors, administration of A-674563 at 40 mg/kg per day for 21 days, combined with administration of paclitaxel at 15 mg/kg per day on days 20.24.28, increased the efficacy of paclitaxel compared with paclitaxel monotherapy. [1] A563 also significantly blocked HT1080 xenograft growth in nude mice. [2]
References:
1. Luo Y, Shoemaker AR, Liu X et al. Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther. 2005 Jun;4(6):977-86.
2. Zhu QS, Ren W, Korchin B et al. Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha. Cancer Res. 2008 Apr 15;68(8):2895-903.
| Cell experiment [1]: | |
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Cell lines |
soft tissue sarcoma (STS) cell lines |
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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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0-10 μM; 24, 48, and 72 h |
|
Applications |
In STS cell lines, A-674563 significantly decreased GSK3 and MDM2 phosphorylation in a dose-dependent way. A-674563 induced growth inhibition in a dose-dependent and time-dependent manner, and induced G2 cell cycle arrest and apoptosis. |
| Animal experiment [1]: | |
|
Animal models |
Mice with human fibrosarcoma (HT1080) subcutaneous xenografts |
|
Dosage form |
20 mg/kg/bid, p.o. |
|
Application |
In mice with human fibrosarcoma (HT1080) subcutaneous xenografts, A-674563 inhibited tumor growth and significantly reduced tumor volume at the termination of the study (320.76 ± 86.8) compared with that in control group (667.92 ± 97.41; P < 0.01). |
|
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] Zhu QS, Ren W, Korchin B et al. Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha. Cancer Res. 2008 Apr 15;68(8):2895-903. |
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| Cas No. | 552325-73-2 | SDF | |
| Chemical Name | (2S)-1-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxy-3-phenylpropan-2-amine | ||
| Canonical SMILES | CC1=C2C=C(C=CC2=NN1)C3=CC(=CN=C3)OCC(CC4=CC=CC=C4)N | ||
| Formula | C22H22N4O | M.Wt | 358.44 |
| Solubility | ≥ 4.9mg/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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7899 mL | 13.9493 mL | 27.8987 mL |
| 5 mM | 0.558 mL | 2.7899 mL | 5.5797 mL |
| 10 mM | 0.279 mL | 1.3949 mL | 2.7899 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)
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