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N6022

现货
Catalog No.
B1111
GSNOR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,750.00
现货
5mg
¥ 1,030.00
现货
25mg
¥ 3,340.00
现货
100mg
¥ 6,980.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt414.46
Cas No.1208315-24-5
FormulaC24H22N4O3
Solubility≥20.7mg/mL in DMSO
Chemical Name3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-imidazol-1-ylphenyl)pyrrol-2-yl]propanoic acid
SDFDownload SDF
Canonical SMILESCC1=C(C=CC(=C1)C(=O)N)N2C(=CC=C2C3=CC=C(C=C3)N4C=CN=C4)CCC(=O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

乙醇脱氢酶(ADH)酶的测定

ADH IB、ADH II与ADH IV酶测定实验:酶活性测定使用与Sanghani等人描述的类似条件,通过检测由NAD+还原成NADH的A340的增加值。 将N6022溶解并在含有1N NaOH(1%)的PBS溶液中稀释。 用乙醇作为底物测定N6022对ADH1B和ADH II的IC 50值。 ADH1B的最终测定条件为50mM磷酸钠(pH 7.4)、20μg/ mL ADH1B、2mM NAD+和2mM乙醇,ADH II的最终测定条件为90mM焦磷酸钠(pH8.9)、4.4μg/ mL ADH II、23.6mM NAD+和14.4mM乙醇。 使用己醇作为底物测定N6022对ADH IV的IC 50值。 首先将己醇溶解在DMSO中,使得其可以溶解在测定缓冲液中。 最终测定条件为50mM磷酸钠(pH 7.4)、1.25μg/ mL ADH IV、2mM NAD+、400μM己醇和1%DMSO。

动物实验 [2]:

动物模型

雌性BALB / c小鼠模型

剂量

0.1mg / kg至10mg / kg,尾静脉注射给药、持续1-48小时

应用

N6022处理卵白蛋白(OVA)敏化小鼠,N6022以剂量相关的方式地减少增强的暂停(Penh)和支气管肺泡灌洗液(BALF)嗜酸性粒细胞,同时N6022增加支气管肺泡灌洗液(BALF)亚硝酸盐和血浆环鸟苷酸(cGMP)。 此外,N6022削弱OVA诱导的核因子κB(NFκB)激活和减少乙酰甲胆碱(MCh)诱导分离大鼠气管环收缩。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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, 2157-2168

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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