2. NF-κB
  3. Keap1-Nrf2
  4. KI696

KI696 

Cat. No.: HY-101140 Purity: 99.04%
COA Handling Instructions

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
Solution
10 mM * 1 mL in DMSO USD 715 In-stock
Solid + Solvent
10 mM * 1 mL
ready for reconstitution
 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  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 10 publication(s) in Google Scholar

Other Forms of KI696:

Top Publications Citing Use of Products

    KI696 purchased from MCE. 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].

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

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

    550.63

    Appearance

    Solid

    Formula

    C28H30N4O6S
    CAS No.
    SMILES

    COC1=C(N2C)C(N=N2)=CC([[email protected]](C3=CC(CN(C[[email protected]]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 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 50 mg/mL (90.81 mM; Need ultrasonic)

    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
    10 mM 0.1816 mL 0.9081 mL 1.8161 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    • 2.

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

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

    *All of the co-solvents are available by MCE.
    Purity & Documentation

    Purity: 99.26%

    COA (250 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
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.
    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.

    • Molarity Calculator

    • Dilution Calculator

    The molarity calculator equation

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

    Mass   Concentration   Volume   Molecular Weight *
    = × ×

    The dilution calculator equation

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
    × = ×
    C1   V1   C2   V2

    Keywords:

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

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Salutation

    Applicant Name *

    		 

    Email address *

    Phone number *

    		 

    Organization name *

    Department *

    		 

    Requested quantity *

    Country or Region *

    		      

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    KI696
    Cat. No.:
    HY-101140
    Quantity:
    MCE Japan Authorized Agent:

    Customer Review

    Thank You for Your Feedback!

    Request for HNMR Report

    Please fill out this form to request the QC report. We will send it to your Email address shortly.

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Lot #

    Applicant Name *

    		 

    Email address *

    Phone number

    		 

    Department *

    Organization name *

    		 

    Country or Region *

    Remarks

    Request for HNMR Report

    We have received your request and will respond to you as soon as possible.