KI696

Name: KI696
Brand: MedChemExpress
SKU: HY-101140
Rating: 5.0 (12 reviews)

Cat. No.: HY-101140 Purity: 98.67%: FAQs
Data Sheet SDS COA Handling Instructions

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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

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	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 715	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 190	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 590	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 990	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 1990	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 3500	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 5500	In-stock	Estimated Time of Arrival: December 31
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:

11 Publications Citing Use of MCE KI696

: 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.

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Biological Activity
Protocol
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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]

Cellular Effect

Cell Line	Type	Value	Description	References
Epithelial cell	EC₅₀	16 nM Compound: 7	Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of HO-1 mRNA expression incubated for 6 hrs by RT-PCR method Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of HO-1 mRNA expression incubated for 6 hrs by RT-PCR method	[PMID: 27031670]
Epithelial cell	EC₅₀	22 nM Compound: 7	Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of NQO1 mRNA expression incubated for 6 hrs by RT-PCR method Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of NQO1 mRNA expression incubated for 6 hrs by RT-PCR method	[PMID: 27031670]
Epithelial cell	EC₅₀	27 nM Compound: 7	Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of TXNRD1 mRNA expression incubated for 6 hrs by RT-PCR method Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of TXNRD1 mRNA expression incubated for 6 hrs by RT-PCR method	[PMID: 27031670]
Epithelial cell	EC₅₀	36 nM Compound: 7	Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of GCLM mRNA expression incubated for 6 hrs by RT-PCR method Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from COPD patient assessed as induction of GCLM mRNA expression incubated for 6 hrs by RT-PCR method	[PMID: 27031670]

In Vitro

KI696 (compound 7) exhibits very high affinity for the KEAP1 Kelch domain (ITC K_d=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.

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.

1799974-70-1

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
10 mM	0.1816 mL	0.9081 mL	1.8161 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)

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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)

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: 99.26%

Select Batch:

Data Sheet (281 KB) SDS (393 KB)

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

Handling Instructions (2659 KB)

References

[1]. Davies TG, et al. Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery. J Med Chem. 2016 Apr 28;59(8):3991-4006. [Content Brief]

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	[1]. Davies TG, et al. Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery. J Med Chem. 2016 Apr 28;59(8):3991-4006. [Content Brief]

Complete Stock Solution Preparation Table

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

KI696 Related Classifications

Metabolic Disease Inflammation/Immunology

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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Other Forms of KI696:

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11 Publications Citing Use of MCE KI696

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