We use analytics and advertising cookies, which you can accept or reject; see our privacy policy.

Current choice:

Fig. 1 · Structure
Cat. No.
A14433
CAS No.
1218942-37-0
Formula
C21H19ClN4O2
Mol. Weight
394.85

Documents & Downloads

GKT137831

Cat. No. A14433 CAS 1218942-37-0

NOX1/4 inhibitor

GKT137831 is a first in class inhibitor targeting NOX1 and NOX4 enzymes.

In Stock

Publications for GKT137831

1 publication citing this product

  1. Chia-Hui Huang, .et al. , Toxicol Appl Pharmacol, 2020, Apr 17;397:115013 PMID: 32305283
Notify me when the price drops

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

Free Aliquoting for Your Order

Tell us your preferred amount per vial. We’ll confirm the options.

Biological Activity

Bioactivity / Mechanism

GKT137831 is used as a NOX1/4-directed research probe, but ROS-assay interference complicates mechanistic attribution. At 100 μM it interfered with NOX-free MCLA and peroxidase/Amplex Red readouts. In primary hepatic stellate cells, 20 μM GKT137831 reduced the Ang II-stimulated collagen reporter without reducing Rac1 activity. These findings do not establish direct NOX binding or isoform selectivity. [1,2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
NOX1 Ki 110 nM
NOX4 Ki 140 nM

In Vitro Studies

In WT and SOD1 G37R mouse hepatic stellate cells, GKT137831 (20 μM, 24 hours) reduced the collagen α1(I)-GFP response to Ang II. Rac1 activity was unchanged by the compound, limiting interpretation of the response as upstream Rac1 inhibition. [2]

ROS-assay interference controls

Biochemical assay · Cell-free ROS detection systems, including NOX-free MCLA auto-oxidation and peroxidase/Amplex Red controls [1]

At 100 μM, GKT137831 altered ROS-detection signals in NOX-free controls. This limits target attribution from these assays; it does not establish absence of all NOX binding.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
MCLA auto-oxidation and peroxidase/Amplex Red readouts without NOXqualitative response Substantial interference in both assays[1]
Xanthine oxidase-coupled peroxide signal versus PMS-NADH superoxide assayqualitative response Strong reduction of the peroxide-coupled signal; no significant superoxide-scavenging effect attributed to GKT137831[1]

Literature-Reported Treatment Conditions

Treatment concentration
100 μM
Method
Cell-free assay-interference and ROS-scavenging comparison
Co-treatment
No therapeutic combination
Reported limits
Exact Figure 4B incubation details and replicate n are not specified in the reviewed main-text description; no percentage was digitized.
Methods and source locations

Compound reported in the paper: GKT137831; Compound label in the paper: GKT137831

Reported effects apply to the experimental material and model; they do not validate an Adooq lot.

Figures 1A and 4A–B; §§2.1, 2.4, 2.10, 3.3

MCLA auto-oxidation and peroxidase/Amplex Red readouts without NOX: NOX-free probe controls, including NADPH in the peroxidase/Amplex Red control — Figure 4B; §3.3

Xanthine oxidase-coupled peroxide signal versus PMS-NADH superoxide assay: Parallel cell-free detection systems; superoxide assay used SOD as positive control — Figure 4A; §§2.4 and 3.3

Collagen-reporter and Rac1 responses in primary stellate cells

Cell-based study · Primary hepatic stellate cells from WT and SOD1 G37R mice; collagen α1(I)-GFP reporter for the collagen readout [2]

GKT137831 reduced the Ang II-stimulated collagen-GFP response in WT and SOD1-mutant HSCs, while Rac1 activity remained elevated. These are cellular responses rather than a direct binding assay.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Collagen α1(I)-GFP-positive HSCsqualitative response Reduced Ang II-induced reporter response with GKT137831 in both genotypes; n=3 as reported[2]
Ang II-stimulated Rac1 activityqualitative response GKT137831 did not reduce Rac1 activity; n=3 as reported[2]

Literature-Reported Treatment Conditions

Treatment concentration
20 μM
Exposure duration
24 hours
Method
Ang II (10−6 M) stimulation with GKT137831 or vehicle; DMEM changed to 1% FBS after 48 hours
Vehicle
PBS, as reported
Co-treatment
Ang II is the experimental stimulus
Reported limits
Caption n=3 is retained without assigning biological versus technical replicate identity.
Methods and source locations

Compound reported in the paper: GKT137831; Compound label in the paper: GKT137831

Reported effects apply to the experimental material and model; they do not validate an Adooq lot.

Figure 6A–B,E; HSC Isolation, Cell Culture and Treatment; Rac1 Activity Assay

Collagen α1(I)-GFP-positive HSCs: Fluorescence microscopy and quantification of GFP-positive cells — Figure 6A–B and caption

Ang II-stimulated Rac1 activity: Rac1 G-LISA activation assay, luminescence readout — Figure 6E and caption; Rac1 Activity Assay; corresponding Results

In Vivo Studies

Animal liver responses differed by model. Daily intragastric GKT137831 (60 mg/kg) during the last 3 weeks of CCl4 exposure reduced fibrotic readouts in WT and SOD1 G37R mice. In obese HFD-fed mice, oral GKT137831 (40 mg/kg, 3 times weekly for 5 weeks) instead increased steatosis and fibrosis-associated readouts, with no significant liver-weight change. The studies do not establish the cause of this difference. [2,3]

Liver fibrotic readouts during CCl4 injury

Animal study · Male WT and SOD1 G37R mice with CCl4-induced liver injury [2]

Treatment during the second half of ongoing CCl4 exposure reduced fibrotic readouts in both genotypes. This design does not demonstrate efficacy across liver-disease contexts.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Hepatic collagen deposition, α-SMA, collagen α1(I), TIMP-1 and TGF-β1 transcriptsqualitative response Reduced relative to CCl4 plus treatment vehicle; n=5 as reported[2]

Conditions shared by the study groups

Route
Intragastric
Frequency
Daily
Treatment course
Last half of the 6-week CCl4 exposure (3 weeks)
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
GKT137831 during established CCl4 exposure
60 mg/kg		Within-genotype CCl4 plus treatment vehicle; oil-control groups also shownLower collagen staining, α-SMA and fibrogenic transcripts in both genotypes[2]
GKT137831 during established CCl4 exposure
Model: Six-week-old male WT C57BL/6J and SOD1 G37R mice on a C57BL/6 background
Reported limits: GKT137831 dosing-vehicle composition is not specified in the reviewed main Methods; corn oil refers to CCl4 vehicle and is not assigned to GKT137831.
Methods and source locations

Compound reported in the paper: GKT137831; Compound label in the paper: GKT137831

Reported effects apply to the experimental material and model; they do not validate an Adooq lot.

Mice; Figure 3A–E and caption; corresponding Results

Hepatic collagen deposition, α-SMA, collagen α1(I), TIMP-1 and TGF-β1 transcripts: Sirius red staining/area quantification, α-SMA immunohistochemistry and immunoblot, quantitative real-time PCR — Figure 3A–E and caption

GKT137831 during established CCl4 exposure · Mice; Figure 3A–E and caption

Opposing liver outcome in diet-induced obesity

Animal study · Male C57BL/6 mice fed a HFD for 15 weeks, with a 5-week GKT137831 course [3]

In this HFD model, GKT137831 worsened steatosis and fibrosis-associated outcomes rather than showing the direction observed during CCl4 injury.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Liver pathology, antioxidant-defense genes and liver weightqualitative response Reduced antioxidant-defense transcripts, increased steatosis and fibrosis-associated readouts, with no significant liver-weight change; n=12 per group in Figure 13[3]

Conditions shared by the study groups

Route
Oral gavage
Frequency
3 times per week
Treatment course
5 weeks
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
GKT137831 in obese HFD-fed mice
40 mg/kg		Vehicle-treated HFD-fed mice; Figure 13 labels n=12 per groupGreater steatosis, lymphocytic infiltrates and fibrosis-associated readouts; liver weight showed no significant change[3]
GKT137831 in obese HFD-fed mice
Model: Male C57BL/6 mice fed a HFD for 15 weeks, with a 5-week GKT137831 course
Reported limits: In vivo vehicle composition and animal-study lot are not specified in the acquired main text or reviewed supplementary method sections. Sigma-Aldrich is named for cellular GKT137831 but is not assumed to establish the animal lot.
Methods and source locations

Compound reported in the paper: GKT137831; Compound label in the paper: GKT137831

Reported effects apply to the experimental material and model; they do not validate an Adooq lot.

Figure 13A–H and caption; corresponding Results; Supplemental Methods: Mice, Histology

Liver pathology, antioxidant-defense genes and liver weight: qPCR and representative H&E/Picrosirius red histology; mean ± SEM, Student’s t test for A–D and G — Figure 13A–H; corresponding Results

GKT137831 in obese HFD-fed mice · Figure 13A–H and caption; Results paragraph immediately preceding Figure 13; Supplemental Methods: Mice and Histology

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 1218942-37-0
Applications NOX1/4 inhibitor
Formula C21H19ClN4O2
Molecular Weight 394.85
SMILES
CN1C(=O)C=C2C(=C1C3=CC(=CC=C3)N(C)C)C(=O)N(N2)C4=CC=CC=C4Cl

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO Warmed: 72 mg/mL (182.34 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
8 mg/mL
Vehicle
2% DMSO+2% Tween 80+30% PEG 300+ddH2O

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Reis J, Massari M, Marchese S, et al. A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action Redox biology (2020). PMID: 32105983 DOI: 10.1016/j.redox.2020.101466 Source material
  2. [2] Aoyama T, Paik YH, Watanabe S, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent Hepatology (Baltimore, Md.) (2012). PMID: 22806357 DOI: 10.1002/hep.25938 Source material
  3. [3] Greatorex S, Kaur S, Xirouchaki CE, et al. Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity The Journal of clinical investigation (2024). PMID: 38060313 DOI: 10.1172/jci162533 Source material

Publications

1 publication citing this product

  1. Chia-Hui Huang, .et al. , Toxicol Appl Pharmacol, 2020, Apr 17;397:115013 PMID: 32305283

Added to your cart

View Cart Checkout
Loading...