A-674563

Catalog No.S2670

A-674563 Chemical Structure

Molecular Weight(MW): 358.44

A-674563 is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.

Size Price Stock Quantity  
In DMSO USD 510 In stock
USD 170 In stock
USD 320 In stock
USD 570 In stock
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3 Customer Reviews

  • Cell survival was determined using a WST-1 assay in the human lung cancer cells A549 A. and NCI-H358 B. following treatment with either an AKT1 specific inhibitor, A-674563 (black circle and line) or a pan-AKT inhibitor MK-2206 (gray square and line). *p < 0.05.

    Oncotarget, 2016, 7(3):3297-316. A-674563 purchased from Selleck.

    Akt1 and Akt2 isoforms are required for Wnt5a-induced RhoA activity. a, c Human osteosarcoma cells MG-63 (a) and U20S (c), serum-deprived for 24 h, were pre-treated with 10 nmol/L MK-2206 (Akt inhibitor) for 1 h, were incubated with 100 ng/mL Wnt5a and harvested at 30 min after the start of Wnt5a treatment. The relative RhoA activity was normalized to the average value of LY294002/Wnt5a-untreated group. b, d Serum-deprived MG-63 (b) and U20S cells (d) were pre-treated with 10 nmol/L A-674563 (Akt1 inhibitor) and 10 nmol/L CCT128930 (Akt2 inhibitor) for 1 h, then were incubated with 100 ng/mL Wnt5a and harvested at 30 min after the start of Wnt5a treatment. Data were presented as mean ± SD of 3 determinations. The relative RhoA activity was normalized to the average value of each inhibitor-untreated group

    Cancer Cell Int, 2017. A-674563 purchased from Selleck.

  • B cells were pre-treated with the indicated concentrations of A-674563 for 1h prior to R848 treatment (500 ng/ml).  Thymidine incorporation was analyzed 24h later.

    2012 Lee lay hoon from National University of Singapore. A-674563 purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description A-674563 is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.
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.
Targets
Akt1 [1]
(Cell-free assay)
PKA [1]
(Cell-free assay)
CDK2 [1]
(Cell-free assay)
GSK-3β [1]
(Cell-free assay)
ERK2 [1]
(Cell-free assay)
11 nM(Ki) 16 nM(Ki) 46 nM(Ki) 110 nM(Ki) 260 nM(Ki)
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]

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]

Protocol

Kinase Assay:[1]
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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.
Cell Research:[1]
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  • Cell lines: MiaPaCa-2 cells
  • Concentrations: 0-30 μM
  • Incubation Time: 48 hours
  • 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 manufacturer's 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Fasted mice
  • Formulation: 5% dextrose.
  • Dosages: 20 or 100 mg/kg
  • Administration: A-674563 is administered 30 minutes before the 1 g/kg glucose challenge.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 72 mg/mL (200.87 mM)
Water 72 mg/mL (200.87 mM)
Ethanol 18 mg/mL (50.21 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 Information

Molecular Weight 358.44
Formula

C22H22N4O

CAS No. 552325-73-2
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID