| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
NOX1 NOX4
GKT136901 hydrochloride targets NADPH oxidase isoforms NOX1 and NOX4, enzymes that are central to reactive oxygen species (ROS) generation in vascular, metabolic, and inflammatory pathways. NOX1 and NOX4 are members of the NADPH oxidase family that catalyze the production of superoxide and hydrogen peroxide. By inhibiting NOX1 and NOX4 with Ki values of 160 nM and 165 nM respectively, GKT136901 hydrochloride reduces ROS production and oxidative stress. The compound also functions as a direct peroxynitrite scavenger. |
|---|---|
| ln Vitro |
The increase in O2 caused by high d-glucose is significantly reduced by GKT136901 hydrochloride (10 μM; 30 min).- generation as well as H2O2 generation in MPT cells [4]. In MPT cells, the effects of high D-glucose on p38MAP kinase activation are eliminated by GKT136901 hydrochloride (10 μM; 30 min) [4]. In HBMEC, GKT136901 hydrochloride (10 μM; 2 hours) reduces oxidative stress caused by methamphetamine (METH) [5]. HBMEC is protected from METH-induced blood-brain barrier (BBB) dysfunction by GKT136901 hydrochloride (10 μM; 2 hours) [5].
In vitro, GKT136901 hydrochloride demonstrates potent inhibition of NOX1 and NOX4 with Ki values of 160 nM and 165 nM, respectively. The compound inhibits METH-induced ROS production and acts as a selective peroxynitrite scavenger. GKT136901 hydrochloride shows concentration-dependent inhibition of NADPH oxidase activity in biochemical assays using purified enzyme preparations. The compound exhibits anti-inflammatory activity in cellular models. |
| ln Vivo |
In a mouse model of type 2 diabetes, GKT136901 hydrochloride (30-90 mg/kg; administered orally daily for 16 weeks) has renoprotective properties[6].
In vivo, GKT136901 hydrochloride has been evaluated for its anti-inflammatory and neuroprotective effects. The compound is orally active and has been studied in models of neurodegenerative diseases and diabetic nephropathy. GKT136901 hydrochloride reduces oxidative stress and inflammation in vivo. Detailed efficacy studies in animal models have been reported, demonstrating the compound's potential for therapeutic applications. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for GKT136901 hydrochloride typically involves measuring NOX1 or NOX4 activity using lucigenin-enhanced chemiluminescence or Amplex Red assays. Purified enzyme or membrane fractions containing NOX1 or NOX4 are incubated with varying concentrations of GKT136901 hydrochloride (0.001-100 µM) in assay buffer at 37°C. The reaction is initiated by adding NADPH, and ROS production is measured. Ki values are calculated from dose-response curves.
|
| Cell Assay |
For in vitro cell-based assays, cells expressing NOX1 or NOX4 are cultured and treated with GKT136901 hydrochloride at concentrations ranging from 0.1-100 µM for 1-24 hours. ROS production is measured using fluorescent probes such as DCFH-DA. NADPH oxidase activity is assessed by measuring superoxide or hydrogen peroxide production. Inflammatory cytokine levels are measured by ELISA. Cell viability is assessed using MTT or CCK-8 assays.
|
| Animal Protocol |
Animal/Disease Models: Male db/db and db/m mice (8 weeks)[6]
Doses: 30, 90 mg/kg Route of Administration: Daily po for 16 weeks Experimental Results: decreased albuminuria, thiobarbituric acid-reacting substances (TBARS) and renal ERK1 /2 phosphorylation and preserved renal structure in diabetic mice. Had no effect on plasma glucose, BP (blood pressure), and body weight. In vivo animal studies for GKT136901 hydrochloride are conducted using models of neurodegenerative diseases, diabetic nephropathy, or inflammatory conditions. The compound is administered orally at doses ranging from 1-50 mg/kg for 1-4 weeks. ROS production and oxidative stress markers are measured in tissues. Inflammatory cytokine levels are assessed. Disease progression is evaluated by histopathology and functional assessments. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of GKT136901 hydrochloride have been partially characterized. The compound is orally active. Molecular weight is 344.84 g/mol and the molecular formula is C₁₄H₁₂Cl₂N₄OS·HCl. The compound is supplied as a hydrochloride salt. Detailed pharmacokinetic parameters such as half-life, Cmax, and protein binding have not been extensively reported.
|
| Toxicity/Toxicokinetics |
Toxicology data for GKT136901 hydrochloride are limited. As a research compound, it has not been fully evaluated for safety. The compound's mechanism of NOX1/NOX4 inhibition suggests potential effects on ROS signaling and immune function, which would require careful safety assessment. Standard toxicological endpoints including body weight, organ weights, clinical chemistry, and histopathology should be evaluated. The compound is intended for research use only.
|
| References |
|
| Additional Infomation |
GKT136901 hydrochloride is a potent, selective, and orally active NOX1/NOX4 inhibitor with Ki values of 160 nM and 165 nM, respectively. It also functions as a peroxynitrite scavenger and exhibits anti-inflammatory activity. The compound is used in research on neurodegenerative diseases and diabetic nephropathy. GKT136901 hydrochloride is intended for research use only and is not approved for therapeutic applications.
|
| Molecular Formula |
C19H20CL2N4O2
|
|---|---|
| Molecular Weight |
407.2937
|
| Exact Mass |
402.065
|
| CAS # |
1254507-01-1
|
| Related CAS # |
GKT136901;955272-06-7
|
| PubChem CID |
155977664
|
| Appearance |
Light yellow to light brown solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
675
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=C([H])C([H])=C([H])C([H])=C1N1C(C2([H])C([H])(C([H])([H])[H])N(C([H])([H])C3=C([H])C([H])=C([H])C([H])=N3)C(C([H])([H])C2([H])N1[H])=O)=O.Cl[H]
|
| InChi Key |
BIXDBKGUQPCHLH-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H15ClN4O2.ClH/c1-12-18-15(10-17(25)23(12)11-13-6-4-5-9-21-13)22-24(19(18)26)16-8-3-2-7-14(16)20;/h2-10,22H,11H2,1H3;1H
|
| Chemical Name |
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 62.5 mg/mL (154.99 mM)
H2O: 4 mg/mL (9.92 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4553 mL | 12.2763 mL | 24.5525 mL | |
| 5 mM | 0.4911 mL | 2.4553 mL | 4.9105 mL | |
| 10 mM | 0.2455 mL | 1.2276 mL | 2.4553 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
