2. PI3K/Akt/mTOR
  3. Akt
  4. A-674563

A-674563 is an orally active and selective Akt1 inhibitor with a Ki of 11 nM.

For research use only. We do not sell to patients.

A-674563 Chemical Structure

A-674563 Chemical Structure

CAS No. : 552325-73-2

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 154 In-stock
Solution
10 mM * 1 mL in DMSO USD 154 In-stock
Solid
1 mg USD 60 In-stock
5 mg USD 140 In-stock
10 mg USD 220 In-stock
25 mg USD 440 In-stock
50 mg USD 650 In-stock
100 mg USD 1050 In-stock
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Customer Review

Based on 5 publication(s) in Google Scholar

Other Forms of A-674563:

A-674563 Related Antibodies

Top Publications Citing Use of Products

    A-674563 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2016 May 17;7(20):29131-42.  [Abstract]

    A674563 selectively inhibits FLT3-ITD. Inhibitory Effects of A674563 against auto-phosphorylation of FLT3 wt/mt kinases in the FLT3 wt/mt transformed BaF3 isogenic cell lines.

    View All Akt Isoform Specific Products:

    View All Isoforms
    Akt Akt1 Akt2 Akt3

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    A-674563 is an orally active and selective Akt1 inhibitor with a Ki of 11 nM.

    IC50 & Target[1]

    Akt1

    11 nM (Ki)

    PKA

    16 nM (Ki)

    CDK2

    46 nM (Ki)

    GSK3β

    110 nM (Ki)

    ERK2

    260 nM (Ki)

    PKCδ

    360 nM (Ki)

    RSK2

    580 nM (Ki)

    MAPK-AP2

    1.1 μM (Ki)

    PKCγ

    1.2 μM (Ki)

    Chk1

    2.6 μM (Ki)

    CK2

    5.4 μM (Ki)

    SRC

    13 μM (Ki)

    In Vitro

    A-674563 slows proliferation of tumor cells with an EC50 of 0.4 μM[1].
    A563 (0-10 µM) significantly decreases GSK3 and MDM2 phosphorylation in STS cells. A563 shows inhibitory effect on all STS cell lines, with IC50 values at 48 hours ranging from 0.22 µM (SW684) to 0.35 µM (SKLMS1). A563 induces G2 cell cycle arrest and apoptosis in STS cells. A563 (1 µM/12 hr) upregulates the expression of GADD45A independent of p53[2].
    A-674563 (10-1000 nM) is anti-proliferative and cytotoxic in cultured human melanoma cells, induces melanoma cell apoptotic death, inhibited by caspase inhibitors, and inhibits melanoma cells via Akt-dependent and -independent mechanisms[3].
    A-674563 is cytotoxic and anti-proliferative when added to U937 and AmL progenitor cells, activates caspase-3/9 and apoptosis in U937 and AmL progenitor cells, and manipulates other signalings in AmL cells whiling blocking Akt[4].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    A-674563 Related Antibodies
    In Vivo

    A-674563 (40 mg/kg/d, p.o.) shows no significant monotherapy activity, but the efficacy of the combination therapy (A-674563+paclitaxel) is significantly improved in the PC-3 prostate cancer xenograft model. A-674563 (20, 100 mg/kg) increases plasma insulin in an oral glucose tolerance test[1].
    A563 (20 mg/kg/bid; p.o.) exhibits slow tumor growth and a significant difference in tumor volume without significant weight loss of mice. A563-treated tumors express increased levels of GADD45α and decreased levels of PCNA (a nuclear marker for proliferation). Additionally, TUNEL assay staining levels (marker for apoptosis) increase in the A563-treated specimens[2].
    A-674563 (25, 100 mg/kg, lavage daily) potently inhibits A375 xenograft growth in mice[3].
    A-674563 (15, 40 mg/kg) injection inhibits U937 xenograft in vivo growth, and improves mice survival[4].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Molecular Weight

    358.44

    Formula

    C22H22N4O
    CAS No.
    Appearance

    Solid

    Color

    White to yellow

    SMILES

    N[C@@H](CC1=CC=CC=C1)COC2=CC(C3=CC4=C(C=C3)NN=C4C)=CN=C2
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 83.33 mg/mL (232.48 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.7899 mL 13.9493 mL 27.8987 mL
    5 mM 0.5580 mL 2.7899 mL 5.5797 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    C2

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: 5.75 mg/mL (16.04 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 5.75 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (57.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.08 mg/mL (5.80 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.87%

    COA (245 KB) HNMR (169 KB) LCMS (449 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [1]

    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 μL) is added to each well on the 96-well plates and incubated until the reaction is complete. 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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Immunocompromised male scid mice are at 6 to 8 weeks of age. The 1×106 3T3-Akt1 or 2×106 MiaPaCa-2 and PC-3 cells in 50% Matrigel are inoculated s.c. into the flank. For early treatment studies, mice are randomLy assigned to treatment groups and therapy is initiated the day after inoculation. Ten animals are assigned to each group, including controls. For established tumor studies, tumors are allowed to reach a designated size and mice are assigned to treatment groups of equal tumor size (n=10 mice per group). Tumor size is evaluated by twice weekly measurements with digital calipers. Tumor volume is estimated using the formula: V=L×W2/2. A-443654 is given s.c. in a vehicle of 0.2% HPMC. A-674563 is given orally in a vehicle of 5% dextrose. Gemcitabine and paclitaxel are added to the assay.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.7899 mL 13.9493 mL 27.8987 mL 69.7467 mL
    5 mM 0.5580 mL 2.7899 mL 5.5797 mL 13.9493 mL
    10 mM 0.2790 mL 1.3949 mL 2.7899 mL 6.9747 mL
    15 mM 0.1860 mL 0.9300 mL 1.8599 mL 4.6498 mL
    20 mM 0.1395 mL 0.6975 mL 1.3949 mL 3.4873 mL
    25 mM 0.1116 mL 0.5580 mL 1.1159 mL 2.7899 mL
    30 mM 0.0930 mL 0.4650 mL 0.9300 mL 2.3249 mL
    40 mM 0.0697 mL 0.3487 mL 0.6975 mL 1.7437 mL
    50 mM 0.0558 mL 0.2790 mL 0.5580 mL 1.3949 mL
    60 mM 0.0465 mL 0.2325 mL 0.4650 mL 1.1624 mL
    80 mM 0.0349 mL 0.1744 mL 0.3487 mL 0.8718 mL
    100 mM 0.0279 mL 0.1395 mL 0.2790 mL 0.6975 mL
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    A-674563 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    A-674563552325-73-2A674563A 674563AktPKBProtein kinase BInhibitorinhibitorinhibit

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