1. Cell Cycle/DNA Damage Autophagy Apoptosis
  2. PERK Autophagy Apoptosis
  3. GSK2656157

GSK2656157 is a selective and ATP-competitive inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) with an IC50 of 0.9 nM.

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

GSK2656157 Chemical Structure

GSK2656157 Chemical Structure

CAS No. : 1337532-29-2

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10 mM * 1 mL in DMSO
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50 mg USD 330 In-stock
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Customer Review

Based on 42 publication(s) in Google Scholar

Top Publications Citing Use of Products

38 Publications Citing Use of MCE GSK2656157

WB

    GSK2656157 purchased from MedChemExpress. Usage Cited in: J Steroid Biochem Mol Biol. 2021, 105893.

    Pretreatment with GSK2656157 (1 μM) alleviated the NEFA-induced increase in protein abundance and mRNA levels of PERK, eIF2α, ATF4, and CHOP vis a vis treatment with 1.2 mM NEFA alone.

    GSK2656157 purchased from MedChemExpress. Usage Cited in: Oxid Med Cell Longev. 2020 Jul 27;2020:8291413.  [Abstract]

    GSK2656157 not only inhibits the expression of p-PERK, but also reduces the expression of NRF2 in the nucleus (n-NRF2) and total NRF2 (t-NRF2) proteins.

    GSK2656157 purchased from MedChemExpress. Usage Cited in: J Neuroinflammation. 2017 May 11;14(1):104.  [Abstract]

    GSK2656157 treatment suppresses PERK autophosphorylation and TXNIP expression; STF083010 treatment inhibits IRE1α endonuclease activity and TXNIP expression. Representative Western blot and densitometric quantification of protein band optical densities for p-PERK, p-eIF2α/eIF2α, ATF-5, ChREBP, splicing XBP1 (sXBP1) and TXNIP. TXNIP expression is downregulated by GSK2656157 and STF083010 treatment.

    GSK2656157 purchased from MedChemExpress. Usage Cited in: Int J Mol Sci. 2017 Apr 18;18(4). pii: E854.  [Abstract]

    GSK2656157 treatment suppresses TXNIP expression and the number of TUNEL-positive cells. TXNIP expression is significantly suppressed by the GSK2656157 (300 μg) treatment.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    GSK2656157 is a selective and ATP-competitive inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) with an IC50 of 0.9 nM.

    IC50 & Target[1]

    EIF2AK3 (PERK)

    0.9 nM (IC50)

    EIF2AK1 (HRI)

    460 nM (IC50)

    BRK

    905 nM (IC50)

    EIF2AK2 (PKR)

    905 nM (IC50)

    MEKK3

    954 nM (IC50)

    Aurora B

    1259 nM (IC50)

    KHS

    1764 nM (IC50)

    LCK

    2344 nM (IC50)

    MLK2

    2796 nM (IC50)

    MEKK3

    2847 nM (IC50)

    ALK5

    3020 nM (IC50)

    MLCK2

    3039 nM (IC50)

    EIF2AK4(GCN2)

    3162 nM (IC50)

    c-MER

    3431 nM (IC50)

    PI3Kγ

    3802 nM (IC50)

    WNK3

    5951 nM (IC50)

    LRRK2

    6918 nM (IC50)

    ROCK1

    7244 nM (IC50)

    MSK1

    8985 nM (IC50)

    NEK1

    9807 nM (IC50)

    AXL

    9808 nM (IC50)

    JAK2

    24547 nM (IC50)

    In Vitro

    GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2α, ATF4, and CHOP with an IC50?in the range of 10-30 nM in the BxPC3 pancreatic tumor cell line. Cells that are exposed to 1 μM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis[1].
    GSK2656157 causes the activation of another eIF2α kinase to compensate for the loss of PERK activity in HT1080 cells. GSK2656157 inhibits the growth of the HT1080 cells[2].
    GSK2656157 inhibits LPS-induced IL-1β production, LPS-induced Caspase 1 activation and LPS-induced eIF-2α phosphorylation, but does not inhibit LPS-induced TNF-α production[3].

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

    In Vivo

    GSK2656157 (1.5-150 mg/kg, p.o.) results in dose-dependent inhibition of phospho-PERK Thr980, with more than 80% inhibition at 50 and 150 mg/kg. GSK2656157 (50-150 mg/kg, p.o.) results in dose-dependent inhibition of tumor growth in human tumor xenograft models[1].

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

    Molecular Weight

    416.45

    Formula

    C23H21FN6O

    CAS No.
    Appearance

    Solid

    Color

    Off-white to light yellow

    SMILES

    CC1=CC=CC(CC(N2CCC3=C2C=CC(C4=CN(C)C5=NC=NC(N)=C54)=C3F)=O)=N1

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvent & Solubility
    In Vitro: 

    1M HCl : 100 mg/mL (240.12 mM; ultrasonic and adjust pH to 1 with HCl)

    DMSO : 8.33 mg/mL (20.00 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 2.4012 mL 12.0062 mL 24.0125 mL
    5 mM 0.4802 mL 2.4012 mL 4.8025 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, 1 years; -20°C, 6 months. When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

    • 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

    ×
    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    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 0.5 mg/mL (1.20 mM); Clear solution

      This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 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: ≥ 0.5 mg/mL (1.20 mM); Clear solution

      This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 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.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    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:  0.5% HPMC  0.2%Tween80

      Solubility: 4.17 mg/mL (10.01 mM); Suspended solution; Need ultrasonic

    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: 99.66%

    References
    Kinase Assay
    [1]

    BxPC3 (human pancreatic adenocarcinoma) or LL/2 (murine lung carcinoma) cells are treated with DMSO or various concentrations of GSK2656157 for 1 hour, followed by addition of 5 μg/mL tunicamycin or 1 μM thapsigargin for an additional 6 hours to induce endoplasmic reticulum-stress. Cells are lysed in cold radioimmunoprecipitation assay (RIPA) buffer [150 mM NaCl, 50 mM Tris-Cl pH 7.5, 0.25% sodium deoxycholate, 1% NP-40, protease inhibitors, and 100 mM sodium orthovanadate]. Clarified lysates are resolved by SDS-PAGE and transferred to nitrocellulose membrane using NuPAGE system. Blots are incubated with antibodies to total PERK, p-eIF-2α Ser51, total eIF-2α, ATF4, and CHOP. IRDye700DX-labeled goat anti-mouse immunoglobulin G (IgG), IRDye800-CW donkey anti-goat IgG, and IRDye800-CW goat anti-rabbit IgG are used as secondary antibodies. Proteins are detected on the Odyssey Infrared Imager.

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

    Cell Assay
    [1]

    BxPC3 cells are treated with DMSO or 1 μM GSK2656157 for 1 hour before adding 5 μg/mL tunicamycin for an additional hour. Cells are metabolically labeled with 125 μCi 35S-methionine for the subsequent 1 hour. Cells are lysed in cold RIPA buffer and lysates are resolved by SDS-PAGE, followed by exposure to a phosphorimager screen. Control cells are also pretreated with 100 μM cyclohexamide for 1 hour followed by metabolic labeling. Radioisotope incorporation is quantitated using ImageQuant 5.2 software.

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

    Animal Administration
    [1]

    Exponentially growing HPAC (5×106 cells/mouse), Capan-2 (10×106 cells/mouse), or NCI-H929 (1×6 cells/mouse) cells are implanted subcutaneously into the right flank of 8- to 12-week-old female SCID mice. Similarly, 10×106 BxPC3 cells per mouse are implanted in female nude mice. When the tumors reached approximately 200 mm3 in size, the animals are weighed, and block randomized according to tumor size into treatment groups of 8 mice each. Mice are dosed orally with the formulating vehicle or GSK2656157. Mice are weighed and tumors measured by calipers twice weekly. Tumor volumes are calculated. The percentage of tumor growth inhibition is calculated on each day of tumor measurement using the formula: 100× [1 − (average growth of the compound-treated tumors/average growth of vehicle-treated control tumors)].

    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, 1 years; -20°C, 6 months. When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO / 1M HCl 1 mM 2.4012 mL 12.0062 mL 24.0125 mL 60.0312 mL
    5 mM 0.4802 mL 2.4012 mL 4.8025 mL 12.0062 mL
    10 mM 0.2401 mL 1.2006 mL 2.4012 mL 6.0031 mL
    15 mM 0.1601 mL 0.8004 mL 1.6008 mL 4.0021 mL
    1M HCl 25 mM 0.0960 mL 0.4802 mL 0.9605 mL 2.4012 mL
    30 mM 0.0800 mL 0.4002 mL 0.8004 mL 2.0010 mL
    40 mM 0.0600 mL 0.3002 mL 0.6003 mL 1.5008 mL
    50 mM 0.0480 mL 0.2401 mL 0.4802 mL 1.2006 mL
    60 mM 0.0400 mL 0.2001 mL 0.4002 mL 1.0005 mL
    80 mM 0.0300 mL 0.1501 mL 0.3002 mL 0.7504 mL
    100 mM 0.0240 mL 0.1201 mL 0.2401 mL 0.6003 mL
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    GSK2656157 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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    Cat. No.:
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