GKT137831 |
| Catalog No.GC11882 |
GKT137831(GKT137831)은 Kis가 각각 140 및 110 nM인 선택적 NADPH 산화효소(NOX1/4) 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1218942-37-0
Sample solution is provided at 25 µL, 10mM.
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Ki: 140 nM and 110 nM
GKT137831 is a specific dual NADPH oxidase Nox1/Nox4 inhibitor, respectively[1].
Both Nox1 and Nox4 expressed in vascular smooth muscle cells (VSMCs) are targeted to discreet intracellular locations, are differentially regulated in response to growth factors and vascular injury, and are activated by distinct mechanis
In vitro: GKT137831 lowers hypoxia-induced H(2)O(2) release, cell proliferation, and TGF-β1 expression and attenuated reductions in PPARγ in HPAECs and HPASMCs. [2] GKT137831 also is a blockade of oxidative stress in response to hyperglycemia in human aortic endothelial cells. [3]
In vivo: In WT and SOD1mut mice, GKT137831 (60 mg/kg i.g.) prevents liver fibrosis and downregulates markers of oxidative stress, inflammation, and fibrosis. [1] In mouse model of chronic hypoxia exposure, GKT137831 (60 mg/kg/d p.o.) attenuates lung PPARγ and TGF-β1 expression of chronic hypoxia–induced right ventricular hypertrophy, vascular remodeling, lung cell proliferation, and hypoxic alterations [2]. GKT137831 (60 mg/kg/d p.o.) also attenuates diabetes mellitus-stimulated atherosclerosis in diabetic apolipoprotein E-deficient mice. [3] Furtermore, GKT137831 prevents the increase of oxidative stress in angII-infused c-hNox4Tg mice, abolishes Akt-mTOR and NF-κB signaling pathway and lowers cardiac remodeling. [4]
Clinical trial: Clinical study has been conducted.
References:
[1] Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, Molango S, Heitz F, Merlot C, Szyndralewiez C, Page P, Brenner DA. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012 Dec;56(6):2316-27.
[2] Green DE, Murphy TC, Kang BY, Kleinhenz JM, Szyndralewiez C, Page P, Sutliff RL, Hart CM. Circulation. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26.
[3] Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El-Osta A, Andrews KL, Chin-Dusting JP, Touyz RM, Wingler K, Cooper ME, Schmidt HH, Jandeleit-Dahm KA. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013 May 7;127(18):1888-902.
[4] Zhao QD, Viswanadhapalli S2, Williams P2, Shi Q2, Tan C2, Yi X2, Bhandari B2, Abboud HE2. NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways. Circulation. 2015 Feb 17;131(7):643-55.
| Cell experiment [1]: | |
|
Cell lines |
Monolayers of HPAECs and HPASMCs, Pulmonary artery endothelial cells |
|
Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.1–20 μM, 24 hours |
|
Applications |
GKT137831 (5 μM, 20 μM) attenuated hypoxia-induced HPAECs and HPASMCs proliferation. GKT137831 (20 μM) attenuated hypoxia-induced H2O2 generation in HPAECs and HPASMCs. During the entire 72-hour hypoxia exposure, GKT137831 administration during the last 24 hours attenuated hypoxia-induced reductions in HPAEC and HPASMC PPARγ expression. |
| Animal experiment [1-3]: | |
|
Animal models |
C57Bl/6 mice exposed to normoxic or hypoxic conditions for 3 weeks, wild-type (WT) and SOD1G37R mutant C57BL/6J mice, Diabetic apolipoprotein E-deficient mice |
|
Dosage form |
Oral gavage, 30 or 60 mg/kg/d, daily for 10 days |
|
Application |
GKT137831 (30 or 60 mg/kg/d) attenuated chronic hypoxia-induced right ventricular hypertrophy, pulmonary vascular remodeling, increases in vessel wall thickness, and proliferation. GKT137831 attenuated hypoxia-induced reductions in PPARγ and increased in TGF-β1 expression. In WT and SOD1mut mice, GKT137831 (60 mg/kg, intragastric (IG) injection) blocked liver fibrosis and downregulated markers of oxidative stress, inflammation, and fibrosis. In diabetic apolipoprotein E-deficient mice, GKT137831 (60 mg/kg/d, p.o.) attenuated diabetes mellitus-accelerated atherosclerosis. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Green D E, Murphy T C, Kang B Y, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation[J]. American journal of respiratory cell and molecular biology, 2012, 47(5): 718-726. [2]. Aoyama T, Paik Y H, Watanabe S, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent[J]. Hepatology, 2012, 56(6): 2316-2327. [3]. Gray SP1, Di Marco E, Okabe J, Szyndralewiez C, et al. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013 May 7;127(18):1888-902. | |
| Cas No. | 1218942-37-0 | SDF | |
| Chemical Name | 2-(2-chlorophenyl)-4-(3-(dimethylamino)phenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione | ||
| Canonical SMILES | CN(C1=CC=CC(C2=C(C3=O)C(NN3C4=CC=CC=C4Cl)=CC(N2C)=O)=C1)C | ||
| Formula | C21H19ClN4O2 | M.Wt | 394.85 |
| Solubility | ≥ 39.5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5326 mL | 12.663 mL | 25.3261 mL |
| 5 mM | 0.5065 mL | 2.5326 mL | 5.0652 mL |
| 10 mM | 0.2533 mL | 1.2663 mL | 2.5326 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)
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