GKT137831
(Synonyms: 2-(2-氯苯基)-4-[3-(二甲基氨基)苯基]-5-甲基-1H-吡唑并[4,3-C]吡啶-3,6(2H,5H)-二酮,GKT137831; GKT831) 目录号 : GC11882
A dual NOX1/NOX4 inhibitor
Cas No.:1218942-37-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Monolayers of HPAECs and HPASMCs, Pulmonary artery endothelial cells |
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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. |
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Reacting condition |
0.1–20 μM, 24 hours |
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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]: | |
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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 |
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Dosage form |
Oral gavage, 30 or 60 mg/kg/d, daily for 10 days |
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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. |
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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. |
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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. | |
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.
| Cas No. | 1218942-37-0 | SDF | |
| 别名 | 2-(2-氯苯基)-4-[3-(二甲基氨基)苯基]-5-甲基-1H-吡唑并[4,3-C]吡啶-3,6(2H,5H)-二酮,GKT137831; GKT831 | ||
| 化学名 | 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 | ||
| 分子式 | C21H19ClN4O2 | 分子量 | 394.85 |
| 溶解度 | ≥ 39.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。