Art. -Nr.: HY-101140

KI696

23 Cited Publications

Kundenbewertung

Based on 23 publication(s) in Google Scholar

KI696 is a selective KEAP1/NRF2 protein-protein interaction inhibitor with a human K_d value of 1.3 nM. KI696 acts by competitively occupying the NRF2-binding pocket of the KEAP1 Kelch domain. KI696 blocks KEAP1-mediated ubiquitination and degradation of NRF2, promotes the translocation of NRF2 to the nucleus, activates the expression of downstream antioxidant genes, increases intracellular glutathione levels, and alleviates oxidative stress-induced cell damage and inflammatory cell infiltration in the lungs. KI696 reduces ozone-induced pulmonary oxidative damage and inflammatory cell accumulation in rats, and upregulates pulmonary antioxidant genes. KI696 can be used in research related to chronic obstructive pulmonary disease, oxidative stress and inflammation.

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Reinheit: 98.32%
CAS. Nr.: 1799974-70-1
Formel: C₂₈H₃₀N₄O₆S
Molecular Weight:550.63

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

KI696 Chemical Structure

CAS. Nr.: 1799974-70-1

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (23)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

NQO1

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) potently inhibits the interaction between the human KEAP1 Kelch domain and NRF2 peptide in cell-free fluorescence polarization (FP) assays; it binds tightly to the human KEAP1 Kelch domain in cell-free isothermal titration calorimetry (ITC) assays, with a K_d value of 1.3 nM^[1].
KI696 exhibits selective off-target properties and shows no cytotoxicity against BEAS-2B human lung epithelial cells at concentrations up to 10 μM^[1].
KI696 promotes the nuclear translocation of NRF2 in a concentration-dependent manner after 6 h treatment on NHBE cells^[1].
KI696 upregulates the expression of NRF2-dependent genes (NQO1 and GCLM) in NHBE cells in an NRF2-dependent manner; it induces NQO1 enzymatic activity in an NRF2-dependent manner; it increases NQO1 enzymatic activity in a concentration-dependent manner in human lung epithelial BEAS-2B cells, with an EC₅₀ of 12 nM after 48 h of treatment^[1].
KI696 (0.0003-1 μM; 18 h) increases intracellular glutathione levels in a concentration-dependent manner and inhibits tBHP-induced glutathione depletion in NHBE cells after 18 h of pretreatment^[1].
KI696 (incubated for 6 h) upregulates the expression of NRF2-regulated genes (NQO1, TXNRD1, GCLM and HO-1) in COPD-derived bronchial epithelial ALI cells in a concentration-dependent manner, with an EC₅₀ of 22 nM for NQO1 after 6 h of treatment^[1].

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

In Vivo

KI696 (5-50 µmol/kg; i.v.; infusion over 6 hours) dose-dependently activates the NRF2 pathway in the lungs of healthy male Han Wistar rats, with an average EC₅₀ of 36.4 µmol/kg for induction of NRF2-regulated gene expression^[1].
KI696 (10-50 µmol/kg; i.v.; infusion over 6 hours; 24 hours prior to ozone exposure) attenuates ozone-induced pulmonary inflammation and restores depleted lung GSH levels in male Han Wistar rats^[1].

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

Animal Model:

Han Wistar (male, 250-300 g)^[1]
Dosage:

5 µmol/kg; 10 µmol/kg; 25 µmol/kg; 50 µmol/kg
Administration:

i.v.; infusion over 6 hours
Result:

Induced dose-dependent upregulation of pulmonary NRF2-controlled genes with distinct peak fold changes and EC₅₀ values: Nqo1 (37-fold, 44.0 µmol/kg), Ho-1 (17-fold, 25.7 µmol/kg), Txnrd1 (9-fold, 42.6 µmol/kg), Srxn1 (28-fold, 33.8 µmol/kg), Gsta3 (15-fold, 28.4 µmol/kg), Gclc (13-fold, 44.1 µmol/kg).
Yielded a mean EC₅₀ of 36.4 µmol/kg for the panel of detected NRF2-regulated genes.

Animal Model:

Han Wistar (male, 250-300 g, ozone-induced oxidative stress and pulmonary inflammation)^[1]
Dosage:

10 µmol/kg; 35 µmol/kg; 50 µmol/kg
Administration:

i.v.; infusion over 6 hours; 24 hours prior to ozone exposure
Result:

Significantly reduced ozone-induced increases in total cells, neutrophils, and mononuclear cells in bronchoalveolar lavage fluid at 35 µmol/kg.
Restored ozone-induced depletion of lung GSH levels in a dose-dependent manner at 10, 35, and 50 µmol/kg.
Achieved steady-state blood concentrations of 407 nM, 946 nM, and 1437 nM respectively during the 6-hour infusion at 10, 35, and 50 µmol/kg.

Chemical Information

CAS. Nr. 1799974-70-1
Appearance Solid
Molecular Weight 550.63
Formel C₂₈H₃₀N₄O₆S
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (23)

All WB2D/3D Cell Culture and DifferentiationCell Proliferation/Viability AssayBio/Physico-chemical AssayCell Imaging/Staining

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Journal Impact Factor

Cell

BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis. [Abstract]

2019 Jul 11;178(2):330-345.e22. PMID: 31257027

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.
Cell Metab

Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis. [Abstract]

2021 Jan 5;33(1):174-189.e7. PMID: 33357455

KI696 purchased from MedChemExpress. Usage Cited in: Cell Metab. 2021 Jan 5;33(1):174-189.e7. [Abstract]

Representative immunoblot of NRF2, GCLC, and GCLM expression in Calu3 cells pre-treated with 100 nM of KI-696 or vehicle (Veh, 0.1% DMSO) for 48 hrs. b-actin is used as loading control.

KI696 purchased from MedChemExpress. Usage Cited in: Cell Metab. 2021 Jan 5;33(1):174-189.e7. [Abstract]

Evaluation of the death of Calu3 cells pre-treated with 100 nM of KI-696 or vehicle (Veh, 0.1% DMSO) for 48 hrs, followed by culture under cystine replete and starved conditions in the presence and absence of 100 μM BSO (N=3). Cell death was monitored with Sytox Green every 2 hours for 47 hours, followed by AUC calculation.

KI696 purchased from MedChemExpress. Usage Cited in: Cell Metab. 2021 Jan 5;33(1):174-189.e7. [Abstract]

Analysis of relative intracellular Glu levels in the Calu3 cells pre-treated with 100 nM of KI-696 or vehicle (Veh, 0.1% DMSO) for 48 hrs, followed by culture in cystine replete or starved conditions in the presence and absence of 100 μM BSO for 12 hrs.
Nat Cancer

Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer. [Abstract]

2025 Jul;6(7):1263-1282. PMID: 40588523

KI696 purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2025 Jul;6(7):1263-1282. [Abstract]

Brightfield microscopy of Kras^G12D/PEC organoids treated for 7 d with DMSO, SFN or KI696.
Nat Metab

Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells. [Abstract]

2026 Apr;8(4):840-854. PMID: 41946999
Nat Cell Biol

Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance. [Abstract]

2022 Feb;24(2):168-180. PMID: 35165418

KI696 purchased from MedChemExpress. Usage Cited in: Nat Cell Biol. 2022 Feb;24(2):168-180. [Abstract]

Quantification of active nuclear S40-phosphorylated NRF2 (pNRF2) intensity from immunofluorescence stainings of MCF10A-RAS and D2.0R cells cultured on stiff or soft Matrigel substrata. KI696 (10 μM) is a KEAP1 inhibitor used as a positive control. Mean levels in the controls were set to 1, and other samples are relative to these (n=59 (DMSO) n=60 (YM and KI696) cells were imaged for each condition, pooled across two independent experiments; unpaired two-tailed Student’s t-tests).
Redox Biol

A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy. [Abstract]

2021 Nov 11:48:102186. PMID: 34801863
Redox Biol

HEATR1 deficiency promotes pancreatic cancer proliferation and gemcitabine resistance by up-regulating Nrf2 signaling. [Abstract]

2020 Jan;29:101390. PMID: 31785531
Nat Chem Biol

Generation of membrane-permeable cyclic peptides inhibiting protein-protein interaction. [Abstract]

2026 Jun 1. PMID: 42225940
Sci Adv

Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice. [Abstract]

2021 May 26;7(22):eabe7548. PMID: 34039599
Sci Adv

Iron-sulfur cluster deficiency can be sensed by IRP2 and regulates iron homeostasis and sensitivity to ferroptosis independent of IRP1 and FBXL5. [Abstract]

2021 May 26;7(22):eabg4302. PMID: 34039609
Cell Death Dis

β2-AR inhibition enhances EGFR antibody efficacy hampering the oxidative stress response machinery. [Abstract]

2023 Sep 19;14(9):613. PMID: 37723219
Cell Death Discov

Redox cycling nitroxide limits cellular iron availability and selectively inhibits iron-sulfur cluster metabolism. [Abstract]

2026 Mar 24. PMID: 41872136
J Ethnopharmacol

Esculetin alleviates murine lupus nephritis by inhibiting complement activation and enhancing Nrf2 signaling pathway. [Abstract]

2022 Apr 24;288:115004. PMID: 35051603
Food Funct

Cardamonin protects against diabetic cardiomyopathy by activating macrophage NRF2 signaling through molecular interaction with KEAP1. [Abstract]

2024 Nov 11;15(22):11083-11095. PMID: 39431579
Food Funct

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis. [Abstract]

2023 May 22;14(10):4905-4920. PMID: 37157847
J Biol Chem

The serine protease DPP9 and the redox sensor KEAP1 form a mutually inhibitory complex. [Abstract]

2024 Nov 28:108034. PMID: 39615677
Adv Redox Res

2025 Sep.
bioRxiv

2026 Jun 11.
bioRxiv

2026 Apr 27.
Res Sq

2026 Jan 9.
bioRxiv

2025 Oct 15.
bioRxiv

Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers. [Abstract]

2025 Jul 30:2025.07.25.666783. PMID: 40766571
bioRxiv

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. [Abstract]

2023 Oct 23:2023.10.20.563287. PMID: 37961514

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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. 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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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 Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Davies T G, 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. Journal of Medicinal Chemistry, 2016, 59(8): 3991-4006.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

KI696

23 Cited Publications

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KI696

MCE Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) KI696

Biologische Aktivität

Chemical Information

Publications (23)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

KI696

MCE Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) KI696

Biologische Aktivität

Chemical Information

Publications (23)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

KI696 Related Classifications

HY-101140 Related Classifications