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

GSK2656157 

Cat. No.: HY-13820 Purity: 99.66%
Handling Instructions

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

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply Now  
10 mM * 1 mL in DMSO USD 92 In-stock
Estimated Time of Arrival: December 31
10 mg USD 84 In-stock
Estimated Time of Arrival: December 31
50 mg USD 300 In-stock
Estimated Time of Arrival: December 31
100 mg USD 540 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 16 publication(s) in Google Scholar

Top Publications Citing Use of Products

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

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

    GSK2656157 purchased from MCE. Usage Cited in: J Neuroinflammation. 2017 May 11;14(1):104.

    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 MCE. Usage Cited in: Oxid Med Cell Longev. 2020 Jul 27;2020:8291413.

    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 MCE. 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.
    • 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].

    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].

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

    Molecular Weight

    416.45

    Formula

    C₂₃H₂₁FN₆O

    CAS No.

    1337532-29-2

    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 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 8.33 mg/mL (20.00 mM; Need ultrasonic)

    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
    10 mM 0.2401 mL 1.2006 mL 2.4012 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    • 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

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

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

    *All of the co-solvents are provided by MCE.
    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

    Purity: 99.66%

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    Keywords:

    GSK2656157GSK 2656157GSK-2656157PERKAutophagyApoptosisProtein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseInhibitorinhibitorinhibit

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