- 貨號 Cat. No.
- S2670
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
A-674563
A-674563 is an Akt1 inhibitor with Ki of 11 nM, modest potent to PKA and >30-fold selective for Akt1 over PKC.
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10mM/1mLIn DMSO |
USD 642 |
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2mg |
USD 214 |
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5mg |
USD 403 |
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10mg |
USD 718 |
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50mg |
USD 2230 |
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100mg |
USD 3402 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
A-674563 is an Akt1 inhibitor with Ki of 11 nM, modest potent to PKA and >30-fold selective for Akt1 over PKC. |
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Targets |
Akt1 |
PKA |
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IC50 |
11 nM (Ki) |
16 nM (Ki) [1] |
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In vitro |
A-674563 is achieved from A-443654 by replacing the indole with a phenyl moiety and getting oral activity. A-674563 slows proliferation of tumor cells with EC50 of 0.4 μM. [1] A-674563 does not inhibit Akt phosphorylation per se, but blocks the phosphorylation of Akt downstream targets in a dose-dependent manner. A-674563 induced Akt blockade results in decreased STS cell downstream target phosphorylation and tumor cell growth inhibiton. A-674563 induces G2 cell cycle arrest and apoptosis in STS cells. [2] |
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In vivo |
20 mg/kg A-674563 increases plasma insulin in an oral glucose tolerance test. A-674563 shows no significant monotherapy tumor inhibitory activity; the efficacy of the combination therapy is significantly improved compared to paclitaxel monotherapy. [1] A674563-treated (20 mg/kg/bid, p.o.) mice exhibits slower tumor growth and more than 50% decrease in the tumor volume at the termination of the study compared with that in control group. [2]A-674563 is identified to have drastically improved PK profile with oral bioavailability of 67% in mouse, but is 70-fold less active than A-443654. [3] |
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Features |
Orally bioavailable compound (achieved by replacing indole of A-443654 with phenyl moiety) and somewhat less selective for Akt over PKA than A-443654. |
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Protocol(Only for Reference)
Kinase Assay: [1]
Akt Kinase Assay |
The kinase assay uses His-Akt1 and a biotinylated mouse Bad peptide as substrate. The kinase assay is carried out at room temperature for 30 minutes in 50 μL of reaction buffer [20 mM HEPES, pH 7.5, 10 mM MgCl2, 0.1% (w/v) Triton X-100, 5 μM ATP (Km = 40 μM), 5 μM peptide (Km = 15 μM), 1 mM DTT, 60 ng of Akt1, and 0.5 μCi of [γ-33P]ATP] in the presence of different concentrations of A-674563. Each reaction is stopped by adding 50 μL of termination buffer (0.1 M EDTA, pH 8.0, and 4 M NaCl). The biotinylated Bad peptides are immobilized on streptavidin-coated FLASH plates. After being washed with PBS-Tween 20 (0.05%), the 33P phosphopeptide captured on the FLASH plates is measured with a TopCount Packard Instruments γ counter. |
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Cell Assay: [1]
Cell lines |
MiaPaCa-2 cells |
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Concentrations |
0-30 μM |
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Incubation Time |
48 hours |
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Method |
The cells on 96-well plates are gently washed with 200 μL of PBS. Alamar Blue reagent is diluted 1:10 in normal growth media. The diluted Alamar Blue reagent (100 M) is added to each well on the 96-well plates and incubated until the reaction is complete as per manufacturers instructions. Analysis is done using an fmax Fluorescence Microplate Reader, set at the excitation wavelength of 544 nm and emission wavelength of 595 nm. Data are analyzed using SOFTmax PRO software provided by the manufacturer. |
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Animal Study: [1]
Animal Models |
Fasted mice |
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Dosages |
20 or 100 mg/kg |
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Administration |
A-674563 is administered 30 minutes before the 1 g/kg glucose challenge. |
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Solubility |
Saline, 30 mg/mL |
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1
References
Download A-674563 SDF
Molecular Weight (MW) |
358.44 |
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Formula |
C22H22N4O
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CAS No. |
552325-73-2 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
72 mg/mL (200 mM) |
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Water |
72 mg/mL (200 mM) |
Ethanol |
18 mg/mL (50 mM) |
In vivo |
Saline, |
30 mg/mL |
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
Chemical Name |
(2S)-1-(5-(3-methyl-1H-indazol-5-yl)pyridin-3-yloxy)-3-phenylpropan-2-amine |
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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.35844 |
3.5844 |
7.1688 |
10.7532 |
Customer Reviews (1)
Click to enlarge |
Rating |
|
Source |
Lee lay hoon from National University of Singapore. A-674563 purchased from Selleck |
Method |
H3 incorporation assay |
Cell Lines |
B cells |
Concentrations |
50-500 nM, 1-50 μM |
Incubation Time |
24 h |
Results |
A-674563 treatment resulted in a reduction of cell proliferation. |
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