| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GKT136901 targets NADPH oxidase 1 (NOX1) and NOX4. It is a dual inhibitor with Ki values of 160 nM for NOX1 and 165 nM for NOX4. It has over 9-fold selectivity for NOX1/4 over NOX2. It does not significantly inhibit a panel of 18 other enzymes and ion channels at 10 μM.
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| ln Vitro |
In high MPT cells, GKT136901 (10 μM; 30 minutes) significantly disconnects O2 induced by D-short circuit. GKT136901 (10 μM; 30 minutes) neutralizes the impact of elevated D- on MPT cell p38MAP activation [4]. Amphetamine production is eliminated and H2O 2 is increased in HBMEC by GKT136901 (10 μM; 2 hours) [4]. HBMEC shells are shielded from METH-induced blood-brain barrier (BBB) dysfunction by GKT136901 (10 μM; 2 hours) [5].
In vitro, GKT136901 potently inhibits NOX1 and NOX4 with Ki values of 160 and 165 nM, respectively. It selectively inhibits NOX1 and NOX4 over NOX2 (Ki = 1,530 nM) and xanthine oxidase (Ki > 30,000 nM). It attenuates ROS generation in various cell-based models. |
| ln Vivo |
In type 2 diabetic mice, GKT136901 (30-90 mg/kg; daily injection for 16 weeks) exhibits renoprotective properties [6].
In vivo, GKT136901 attenuates ROS generation and atherosclerosis in animal models. It decreased CD44 and HA expression in atherosclerotic lesions. It has potential applications in the research of diabetic nephropathy, stroke, and neurodegeneration. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for GKT136901 involve measuring its inhibition of NADPH oxidase activity. These assays typically use purified enzyme or membrane preparations to assess the compound's ability to inhibit ROS production. The Ki values are determined from these enzymatic assays.
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| Cell Assay |
In vitro cell-based assays for GKT136901 involve treating cells with the compound to assess its effects on ROS generation and related cellular processes. Its selectivity for NOX1/4 over other enzymes is confirmed using cell-based assays with specific probes. Its effects on atherosclerosis-related markers are also studied.
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| Animal Protocol |
Animal/Disease Models: Male db/db and db/m mice (8 weeks) [6] ]
Doses: 30, 90 mg/kg Route of Administration: Oral daily for 16 weeks Experimental Results: Albuminuria, sulfur in diabetic mice Phosphorylation of barbituric acid reactive substances (TBARS) and renal ERK1/2 is diminished, and renal structure is preserved. There is no effect on blood sugar, BP (blood pressure) and body weight. In vivo animal experiments for GKT136901 have been conducted in models of atherosclerosis. The compound is typically administered orally, and its effects on lesion formation and ROS generation are assessed. Its potential in diabetic nephropathy, stroke, and neurodegeneration has also been studied in animal models. |
| ADME/Pharmacokinetics |
GKT136901 is orally active, indicating favorable oral bioavailability. It is soluble in DMSO. Its pharmacokinetic properties, such as half-life and clearance, have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GKT136901 is not provided in the search results. As a potent inhibitor of NADPH oxidase, its toxicity profile would be expected to be related to its mechanism of action. Standard toxicological studies would be required for clinical development.
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| References |
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| Additional Infomation |
GKT136901 is a potent, selective, and orally active NOX1/4 inhibitor with potential applications in diabetic nephropathy, stroke, and neurodegeneration. It attenuates ROS generation and atherosclerosis in preclinical models. It is a research compound and has not been approved for clinical use.
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| Molecular Formula |
C19H15CLN4O2
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|---|---|
| Molecular Weight |
366.8
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| Exact Mass |
366.088
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| CAS # |
955272-06-7
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| Related CAS # |
GKT136901 hydrochloride;1254507-01-1
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| PubChem CID |
17027464
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| Appearance |
Off-white to light brown solid powder
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| LogP |
2.885
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
675
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DNKYHHFCPXKFIY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15ClN4O2/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
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| Chemical Name |
2-(2-Chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione
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| Synonyms |
GKT136901 GKT-136901 GKT 136901
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~90.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7263 mL | 13.6314 mL | 27.2628 mL | |
| 5 mM | 0.5453 mL | 2.7263 mL | 5.4526 mL | |
| 10 mM | 0.2726 mL | 1.3631 mL | 2.7263 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.
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