N6022
目录号 : GC16759
An inhibitor of GSNOR
Cas No.:1208315-24-5
Sample solution is provided at 25 µL, 10mM.
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N6022 is a specific and fully reversible inhibitor of S-nitrosoglutathione reductase (GSNOR) with IC50 value of 8nM [1].
N6022 is a first-in-class inhibitor of GSNOR. Inhibition of GSNOR causes the accumulation of GSNO which acts as a vasodilator and anti-inflammatory factor. N6022 presents an IC50 value of 8nM in the GSNO reduction assay and 32nM in the HMGSH oxidation assay. The Ki values are 2.5nM and 3.1nM, respectively. N6022 is selective against GSNOR over other human ADH enzymes. The IC50 values are 21μM, 67μM and 0.5μM for ADH IB, ADH II and ADH IV, respectively. N6022 also shows no effect on the NADPH-dependent enzyme, human carbonyl reductase, with IC50 value of 221μM. Currently, N6022 is under clinical studies for the treatment of inflammatory lung diseases [1].
References:
[1] Green L S, Chun L E, Patton A K, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry, 2012, 51(10): 2157-2168.
| Kinase experiment [1]： | |
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Alcohol dehydrogenase (ADH) Enzyme Assays |
For ADH IB, ADH II, and ADH IV assays, enzyme activity was determined by measuring the increase in A340 due to reduction of NAD+ to NADH using conditions similar to those described by Sanghani et al. N6022 was dissolved and diluted in a PBS solution containing 1 N NaOH (1%). The IC50 values for N6022 versus ADH IB and ADH II were determined with ethanol as the substrate. The final assay conditions for ADH IB were 50 mM sodium phosphate (pH 7.4), 20 μg/mL ADH IB, 2 mM NAD+, and 2 mM ethanol, and the final assay conditions for ADH II were 90 mM sodium pyrophosphate (pH 8.9), 4.4 μg/mL ADH II, 23.6 mM NAD+, and 14.4 mM ethanol. The IC50 value of N6022 against ADH IV was determined using hexanol as a substrate. The hexanol was first dissolved in DMSO so that it could be dissolved in assay buffer. The final assay conditions were 50 mM sodium phosphate (pH 7.4), 1.25 μg/mL ADH IV, 2 mM NAD+, 400 μM hexanol, and 1% DMSO. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/c mice model |
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Dosage form |
0.1 mg/kg to 10 mg/kg, i.v. for 1-48 h |
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Applications |
N6022 dose-dependently decreased enhanced pause (Penh) and Bronchoalveolar lavage fluid (BALF) eosinophils, increased bronchoalveolar lavage fluid (BALF) nitrite and plasma cyclic guanosine monophosphate (cGMP) in ovalbumin (OVA)-sensitized mice. Moreover, N6022 attenuated the OVA-induced increase in nuclear factor kappa B (NFκB) activation and decreased methacholine (MCh)-induced contraction in isolated rat tracheal rings. |
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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, L. S., Chun, L. E., Patton, A. K., Sun, X., Rosenthal, G. J. and Richards, J. P. (2012) Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 51, 2157-21682 2. Blonder, J. P., Mutka, S. C., Sun, X., Qiu, J., Green, L. H., Mehra, N. K., Boyanapalli, R., Suniga, M., Look, K., Delany, C., Richards, J. P., Looker, D., Scoggin, C. and Rosenthal, G. J. (2014) Pharmacologic inhibition of S-nitrosoglutathione reductase protects against experimental asthma in BALB/c mice through attenuation of both bronchoconstriction and inflammation. BMC Pulm Med. 14, 3 |
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| Cas No. | 1208315-24-5 | SDF | |
| 化学名 | 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-imidazol-1-ylphenyl)pyrrol-2-yl]propanoic acid | ||
| Canonical SMILES | CC1=C(C=CC(=C1)C(=O)N)N2C(=CC=C2C3=CC=C(C=C3)N4C=CN=C4)CCC(=O)O | ||
| 分子式 | C24H22N4O3 | 分子量 | 414.46 |
| 溶解度 | ≥ 20.7mg/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 | 2.4128 mL | 12.0639 mL | 24.1278 mL |
| 5 mM | 0.4826 mL | 2.4128 mL | 4.8256 mL |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4128 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet