2. NF-κB
  3. Keap1-Nrf2
  4. KI696

KI696 est une sonde à haute affinité qui perturbe l'interaction Keap1/NRF2. KI696 est un inhibiteur puissant et sélectif de l'interaction KEAP1/NRF2.

KI696 is a high affinity probe that disrupts the Keap1/NRF2 interaction. KI696 is a potent and selective inhibitor of the KEAP1/NRF2 interaction.

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

KI696 Chemical Structure

KI696 Chemical Structure

CAS No. : 1799974-70-1

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 715 In-stock
Solution
10 mM * 1 mL in DMSO USD 715 In-stock
Solid
1 mg USD 190 In-stock
5 mg USD 590 In-stock
10 mg USD 990 In-stock
25 mg USD 1990 In-stock
50 mg USD 3500 In-stock
100 mg USD 5500 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 12 publication(s) in Google Scholar

Other Forms of KI696:

KI696 Related Antibodies

Top Publications Citing Use of Products

    KI696 purchased from MedChemExpress. Usage Cited in: Cell. 2019 Jul 11;178(2):330-345.e22.  [Abstract]

    Western blots showing levels of NRF2, NQO1, and BACH1 in mTC and mTN cells incubated for 24 hr with 5 μM KI-696 peptide to activate NRF2.

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    KI696 is a high affinity probe that disrupts the Keap1/NRF2 interaction. KI696 is a potent and selective inhibitor of the KEAP1/NRF2 interaction[1].

    IC50 & Target

    Target: Keap1-NRF2[1]
    In Vitro

    KI696 (compound 7) exhibits very high affinity for the KEAP1 Kelch domain (ITC Kd=1.3 nM with the exception of the organic anion transporting polypeptide 1B1 (OATP1B1) (IC50=2.5 μM), the bile salt export pump BSEP (IC50=4.0 μM), and the phosphodiesterase PDE3A (IC50=10 μM), no significant cross-reactivity is observed. No cytotoxicity is observed towards BEAS-2B cells with KI696 at concentrations up to 10 μM. KI696 increases NRF2 Nuclear Translocation in Normal Human Bronchial Epithelial cells. KI696 increases mRNA expression of the NRF2-dependent genes NQO1 and GCLM in NHBE cells transfected with the non-targeting siRNA, while NRF2 gene silencing significantly decreases compound activity. KI696 increases NQO1 Activity in an NRF2-Dependent Manner. Treatment with tBHP clearly has a detrimental effect on cell health and appearance while pre-treatment of cells with 1 μM KI696 before the exposure to tBHP maintained cell morphology consistent with the DMSO control. KI696 Induces the Expression of NRF2-Regulated Genes in COPD patient-derived bronchial epithelial cells[1].

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

    KI696 Related Antibodies
    In Vivo

    KI696 induces the expression of each of the Nqo1, Ho-1, Txnrd1, Srxn1, Gsta3, Gclc genes in a dose-dependent manner, with maximum increases over vehicle controls of 37-(Nqo1), 17-(Ho-1), 9-(Txnrd1), 28-(Srxn1), 15-(Gsta3) and 13-fold (Gclc) occurring at the 50 μmol/kg dose. EC50 values are 44.0, 25.7, 42.6, 33.8, 28.4, and 44.1 μmol/kg, respectively, giving an average EC50 value of 36.4±3.4 μmol/kg. KI696 attenuates ozone-Induced pulmonary inflammation. KI696 restores ozone-induced depletion of lung GSH levels. KI696 is administered to rats at 10, 35 and 50 μmol/kg by IV infusion, resulting in steady state compound concentrations in the blood of 407±44 nM, 946±50 nM and 1437±186 nM, respectively, over the 6 hour infusion period. Exposure to ozone 24 hours post-dose produces a significant depletion in lung levels of the anti-oxidant molecule, GSH, which is restored by KI696 in a dose-dependent manner[1].

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

    550.63

    Formula

    C28H30N4O6S
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    COC1=C(N2C)C(N=N2)=CC([C@H](C3=CC(CN(C[C@H]4C)S(=O)(C5=CC=CC=C5O4)=O)=C(C)C=C3)CC(O)=O)=C1
    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 : 50 mg/mL (90.81 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 1.8161 mL 9.0805 mL 18.1610 mL
    5 mM 0.3632 mL 1.8161 mL 3.6322 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
    ×
    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:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

      Solubility: 2.5 mg/mL (4.54 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 2.08 mg/mL (3.78 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

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    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 +
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    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: 99.26%

    COA (251 KB) HNMR (150 KB) RP-HPLC (100 KB) LCMS (337 KB)

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

    Inhibition of the Kelch domain-NRF2 interaction is determined using a fluorescence polarisation-based competition assay in a black 384-well microplate. Each well contained 2 nM 5’-TAMRA-NRF2 peptide (AFFAQLQLDEETGEFL) and 7 nM human KEAP1 (residues 321-609) in 50 µL of assay buffer (50 mM Tris-HCl pH 8.0, 100 mM NaCl, 5 mM MgCl2, 2 mM 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 1 mM DTT, 0.005% BSA, 1% DMSO). After 1 hour at room temperature, fluorescence polarisation (excitation 485 nm/emission 520 nm) is measured using a BMG Pherastar FS plate reader. IC50 values are determined by fitting the data to a four parameter logistic fit[1].

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

    BEAS-2B cells are plated in 384 well black clear-bottomed plates and are incubated overnight (37°C, 5% CO2). On day 2, the plates are centrifuged and 50 nL of compound (KI696) or controls are added to the cells for 48 hours. On day 4, the medium is aspirated from the plate and crude cell lysates are made by using 1X lysis buffer with Complete, Mini, EDTA-free Protease Inhibitor. After lysis, the plates are incubated for 20 minutes at room temperature and the MTT cocktail is prepared for measurement of NQO1 activity. The samples are analyzed on an Envision plate reader, reading absorbance at 570 nm for five individual readings with 10 minute intervals. Product formation is measured kinetically and the pEC50 of NQO1 specific activity induction is calculated by plotting the change in absorbance versus log [compound] followed by 4-parameter fitting[1].

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

    Rats[1]

    To examine the effect of KI696 under conditions of oxidative stress, rats are administered KI696 at 35 µmol/kg (the approximate average EC50 value for gene expression) by IV infusion over 6 hours, and after 24 hours are exposed to ozone (1 ppm for 3 hours). Fifteen minutes following the termination of ozone exposure, the numbers of total cells, neutrophils and mononuclear cells in the bronchoalveolar lavage (BAL) fluid are measured[1].

    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 1.8161 mL 9.0805 mL 18.1610 mL 45.4025 mL
    5 mM 0.3632 mL 1.8161 mL 3.6322 mL 9.0805 mL
    10 mM 0.1816 mL 0.9081 mL 1.8161 mL 4.5403 mL
    15 mM 0.1211 mL 0.6054 mL 1.2107 mL 3.0268 mL
    20 mM 0.0908 mL 0.4540 mL 0.9081 mL 2.2701 mL
    25 mM 0.0726 mL 0.3632 mL 0.7264 mL 1.8161 mL
    30 mM 0.0605 mL 0.3027 mL 0.6054 mL 1.5134 mL
    40 mM 0.0454 mL 0.2270 mL 0.4540 mL 1.1351 mL
    50 mM 0.0363 mL 0.1816 mL 0.3632 mL 0.9081 mL
    60 mM 0.0303 mL 0.1513 mL 0.3027 mL 0.7567 mL
    80 mM 0.0227 mL 0.1135 mL 0.2270 mL 0.5675 mL
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    KI696 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:

    KI6961799974-70-1KI 696KI-696Keap1-Nrf2Inhibitorinhibitorinhibit

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