1. PI3K/Akt/mTOR
  2. Akt
  3. A-443654

A-443654 est un inhibiteur de pan-Akt et a une puissance égale contre Akt1, Akt2, ou Akt3 dans les cellules (Ki=160 pM).

A-443654 is a pan-Akt inhibitor and has equal potency against Akt1, Akt2, or Akt3 within cells (Ki=160 pM).

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

A-443654 Chemical Structure

A-443654 Chemical Structure

CAS No. : 552325-16-3

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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
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10 mM * 1 mL in DMSO USD 275 In-stock
Solid
5 mg USD 250 In-stock
10 mg USD 390 In-stock
25 mg USD 720 In-stock
50 mg USD 1100 In-stock
100 mg USD 1650 In-stock
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Customer Review

Based on 11 publication(s) in Google Scholar

Top Publications Citing Use of Products

    A-443654 purchased from MedChemExpress. Usage Cited in: CNS Neurosci Ther. 2018 Jun;24(6):495-507.  [Abstract]

    Immunohistochemistry results show that the MPP/PHTPP- and G15-induced dramatic decrease in profilin-1 expression is significantly reversed by A-443654.

    A-443654 purchased from MedChemExpress. Usage Cited in: CNS Neurosci Ther. 2018 Jun;24(6):495-507.  [Abstract]

    The MPP/PHTPP-and G15-induced decreases in p-AKT, AKT, and rictor expression are differently affected by mTORC2 activation with A-443654 in the adult female hippocampus.

    A-443654 purchased from MedChemExpress. Usage Cited in: J Steroid Biochem Mol Biol. 2017 Nov;174:96-113.  [Abstract]

    A443654 rescues the methylphenolpyrazole (MPP) + PHTPP-induced downregulation of p-AKT.

    View All Akt Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    A-443654 is a pan-Akt inhibitor and has equal potency against Akt1, Akt2, or Akt3 within cells (Ki=160 pM)[1].

    IC50 & Target

    Akt1

    160 pM (Ki)

    Akt2

    160 pM (Ki)

    Akt3

    160 pM (Ki)

    PKA

    6.3 nM (Ki)

    RSK2

    11 nM (Ki)

    PKCγ

    24 nM (Ki)

    CDK2

    24 nM (Ki)

    PKCδ

    33 nM (Ki)

    GSK3β

    41 nM (Ki)

    ERK2

    340 nM (Ki)

    cKIT

    1.2 μM (Ki)

    Chk1

    2.3 μM (Ki)

    CK2

    2.4 μM (Ki)

    SRC

    2.6 μM (Ki)

    KDR

    3.1 μM (Ki)

    MAPK-AP2

    3.3 μM (Ki)

    Flt1

    3.6 μM (Ki)

    In Vitro

    A-443654 exhibits a Ki of 160 pM, a 30,000-fold improvement in potency versus the initial lead molecule. A-443654 is 40-fold selective for Akt over PKA. A-443654 inhibits Akt1, Akt2, or Akt3 equally within cells. A-443654 reduces the P-GSK3 in a dose-responsive manner in all three cell lines. A-443654 inhibits the proliferation of tumor cells with EC50 of 0.1 μM[1]. A-443654-induced morphological changes occur very rapidly (within 2 to 4 h) in both 10A and 10CA1a cells, with 10CA1a cells more sensitive to A-443654 than the 10A cells. A-443654 alone at 2 μM causes the 10CA1a cells, but not the 10A cells, to detach from the plate after 12 h, whereas 1 μM of A-443654 causes 10CA1a cells to detach from the plate after 12 h. FACScan Analysis of rapamycin and A-443654 effects on DNA content in 10A and 10CA1a cells. In contrast, A-443654 at 2 and 5 μM decreases Bcl-2 levels by 30 to 40% in the 10CA1a cells at 8h. The combination of rapamycin with 2 or 5 μM A-443654, however, markedly decreases Bcl-2 protein levels by appr 40 to 50% in the 10A cells and by appr 70% in the 10CA1a cells, respectively[2]. A-443654 demonstrates the greatest selective effect on the mutant cells compared to the WT cells with greater than 3.5 fold relative growth inhibition of the mutant cells[3].

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

    In Vivo

    A-443654 (7.5 mg/kg/d, s.c.) inhibits tumor growth in the 3T3-Akt1 flank tumor model. A-443654 (50 mg/kg, s.c.) induces apoptosis in 3T3-Akt1 flank tumors. A-443654 (30 mg/kg, s.c.) leads to increased levels of phosphorylated Akt1 in MiaPaCa-2 tumors[1].

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

    Molecular Weight

    397.47

    Formula

    C24H23N5O

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    N[C@H](COC1=CN=CC(C2=CC3=C(NN=C3C)C=C2)=C1)CC4=CNC5=CC=CC=C54

    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 : ≥ 100 mg/mL (251.59 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5159 mL 12.5796 mL 25.1591 mL
    5 mM 0.5032 mL 2.5159 mL 5.0318 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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    ×
    Volume
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    Molecular Weight *

    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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    Volume (final)

    V2

    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    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (6.29 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
    • Protocol 2

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

      Solubility: ≥ 2.5 mg/mL (6.29 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
    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
    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 as per manufacturer's instructions. Analysis is done using an fmaxFluorescence 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.

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

    Animal Administration
    [1]

    Immunocompromised male scid mice are 6 to 8 weeks of age. The 3T3-Akt1 cell line is developed and characterized in our laboratory. 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.

    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 2.5159 mL 12.5796 mL 25.1591 mL 62.8978 mL
    5 mM 0.5032 mL 2.5159 mL 5.0318 mL 12.5796 mL
    10 mM 0.2516 mL 1.2580 mL 2.5159 mL 6.2898 mL
    15 mM 0.1677 mL 0.8386 mL 1.6773 mL 4.1932 mL
    20 mM 0.1258 mL 0.6290 mL 1.2580 mL 3.1449 mL
    25 mM 0.1006 mL 0.5032 mL 1.0064 mL 2.5159 mL
    30 mM 0.0839 mL 0.4193 mL 0.8386 mL 2.0966 mL
    40 mM 0.0629 mL 0.3145 mL 0.6290 mL 1.5724 mL
    50 mM 0.0503 mL 0.2516 mL 0.5032 mL 1.2580 mL
    60 mM 0.0419 mL 0.2097 mL 0.4193 mL 1.0483 mL
    80 mM 0.0314 mL 0.1572 mL 0.3145 mL 0.7862 mL
    100 mM 0.0252 mL 0.1258 mL 0.2516 mL 0.6290 mL
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    A-443654 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.

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    Product Name:
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    Cat. No.:
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