A-674563
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 358.44 |
| Cas No. | 552325-73-2 |
| Formula | C22H22N4O |
| Solubility | insoluble in EtOH; ≥23.8 mg/mL in H2O; ≥4.9 mg/mL in DMSO |
| Chemical Name | (2S)-1-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxy-3-phenylpropan-2-amine |
| SDF | Download SDF |
| Canonical SMILES | CC1=C2C=C(C=CC2=NN1)C3=CC(=CN=C3)OCC(CC4=CC=CC=C4)N |
| Shipping Condition | Ship with blue ice, or upon other requests. |
| General tips | For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. |
| 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. |
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Reacting condition |
0-10 μM; 24, 48, and 72 h |
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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]: | |
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Animal models |
Mice with human fibrosarcoma (HT1080) subcutaneous xenografts |
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Dosage form |
20 mg/kg/bid, p.o. |
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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). |
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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] 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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| Description | A-674563 is an inhibitor of Akt1 with a Ki value of 11 nM. | |||||
| Targets | Akt1 | PKA | CDK2 | GSK-3β | ERK2 | |
| IC50 | 11 nM(Ki) | 16 nM(Ki) | 46 nM(Ki) | 110 nM(Ki) | 260 nM(Ki) | |
Quality Control & MSDS
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Chemical structure
