nor-NOHA (acetate)
(Synonyms: Nω-hydroxy-nor-Arginine) 目录号 : GC10628
nor-NOHA（醋酸盐）（α-氨基酸 N(omega) -Hydroxy-Nor-L-arginine）是一种有效且可逆的选择性精氨酸酶抑制剂，nor-NOHA（醋酸盐）的效力大约是 40 倍NOHA 抑制未受刺激的小鼠巨噬细胞催化 l-精氨酸水解为 l-鸟氨酸（nor-NOHA IC(50) 值 12 77777#177;5µM。
Cas No.:1140844-63-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Preparation Method |
Macrophages (enzymes) were incubated with different stimuli, alone or in the presence of the studied compounds( nor-NOHA (acetate) ) for different times. Aliquots were removed from the medium at selected times and subjected to HPLC analysis and nitrite determination. |
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Reaction Conditions |
0.01-1000uM nor-NOHA (acetate) for 29.0min |
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Applications |
Addition of nor-NOHA (acetate) to mouse macrophages with arginase activity cultured in medium containing L-arginine and L-[U-14C]arginine resulted in a concentration-dependent decrease in L-ornithine formation. |
| Cell experiment [2]: | |
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Cell lines |
K562 cells |
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Preparation Method |
K562 cells were treated with vehicle (DMSO) or increasing concentrations of nor-NOHA (acetate) (0.1 0.5 or 1mM) for 72 h, and cell viability was determined by annexin V/ 7-aad staining. |
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Reaction Conditions |
0.1-1mM nor-NOHA (acetate) for 72h |
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Applications |
nor-NOHA (acetate) had little effect on cell viability under normoxia, it significantly induced apoptosis in a dose-dependent manner under hypoxia, the level of intracellular arginine was reduced upon induction of ARG2 under hypoxia but was restored by nor-NOHA (acetate), confirming the inhibition of arginase activity. |
| Animal experiment [3]: | |
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Animal models |
AIA rats |
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Preparation Method |
AIA rats were treated with nor-NOHA (acetate) (40 mg/kg/ day, IP) for 21 days after the onset of arthritis. A group of untreated AIA rats and a group of healthy rats served as controls. |
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Dosage form |
nor-NOHA (acetate) (40 mg/kg/d, i.p) for 21 days |
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Applications |
nor-NOHA (acetate) treatment could fully restore the aortic response to Ach to that of healthy rats. The results also showed that such beneficial effect was mediated by an increase in NOS activity and EDHF and reduced superoxide anion production. In addition, nor-NOHA (acetate) could decrease IL-6 and VEGF plasma levels in AIA rats. Whereas, the treatment did not modify arthritis severity in AIA rats. |
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References: [1]. Tenu JP, Lepoivre M, et,al. Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages. Nitric Oxide. 1999 Dec;3(6):427-38. doi: 10.1006/niox.1999.0255. PMID: 10637120. [2]. Ng KP, Manjeri A, et,al. The arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) induces apoptosis in leukemic cells specifically under hypoxic conditions but CRISPR/Cas9 excludes arginase 2 (ARG2) as the functional target. PLoS One. 2018 Oct 11;13(10):e0205254. doi: 10.1371/journal.pone.0205254. PMID: 30307989; PMCID: PMC6181325. [3]. Prati C, Berthelot A, et,al. Treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restores endothelial function in rat adjuvant-induced arthritis. Arthritis Res Ther. 2012 May 30;14(3):R130. doi: 10.1186/ar3860. PMID: 22647483; PMCID: PMC3446511. |
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nor-NOHA (acetate) (alpha-amino acid N(omega) -Hydroxy-Nor-L-arginine) is a potent and reversible selective arginase inhibitor, nor-NOHA (acetate) is about 40-fold more potent than NOHA to inhibit the hydrolysis of l-arginine to l-ornithine catalyzed by unstimulated murine macrophages (nor-NOHA IC(50) values 12 ±5µM[4].
nor-NOHA (acetate) effectively induced apoptosis in ARG2-expressing cells under hypoxia but not normoxia. Co-treatment with nor-NOHA (acetate) overcame hypoxia-mediated resistance towards BCR-ABL1 kinase inhibitors. its anti-leukemic activity was independent of ARG2 inhibition. nor-NOHA (acetate) has significant but off-target anti-leukemic activity among ARG2-expressing hypoxic cells[3]. nor-NOHA (acetate) could inhibit the proliferation and induce the apoptosis of HepG2 cells. nor-NOHA (acetate) inhibited the invasion and migration of HepG2 cells. These data indicated that nor-NOHA (acetate) could induce cell apoptosis and inhibit the ability of invasion and migration of HepG2 cells by inhibiting Arg1[1].Supplementation of nor-NOHA (acetate) in BMEC(bovine mammary epithelial cells) reduced cellular proliferation and casein synthesis. Addition of Arg to nor-NOHA (acetate) resulted in cellular proliferation and casein synthesis similar to that of nor-NOHA (acetate) alone. In contrast, addition of Orn to the medium with nor-NOHA (acetate) increased the synthesis of casein and cellular proliferation compared with nor-NOHA (acetate) [6].
nor-NOHA (acetate) treatment could fully restore the aortic response to Ach to that of healthy rats.Such beneficial effect was mediated by an increase in NOS activity and EDHF and reduced superoxide anion production, nor-NOHA (acetate) inhibited arginase activity in aorta with IC50 less than 1 µm [2].In Chinese Holstein cows .The activity of enzymes related to Arg metabolism, milk protein synthesis, and expression of AA transporters was determined. The infusion of nor-NOHA (acetate) decreased the activity of arginase. In addition, the infusion of nor-NOHA (acetate) also reduced protein and fat synthesis in milk but had no effect on milk yield[5].Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA (acetate) suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress[7].
References:
[1]: Li X, Zhu F, et,al. [Arginase inhibitor nor-NOHA induces apoptosis and inhibits invasion and migration of HepG2 cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Apr;33(4):477-482. Chinese. PMID: 28395717.
[2]: Prati C, Berthelot A, et,al. Treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restores endothelial function in rat adjuvant-induced arthritis. Arthritis Res Ther. 2012 May 30;14(3):R130. doi: 10.1186/ar3860. PMID: 22647483; PMCID: PMC3446511.
[3]: Ng KP, Manjeri A, et,al. The arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) induces apoptosis in leukemic cells specifically under hypoxic conditions but CRISPR/Cas9 excludes arginase 2 (ARG2) as the functional target. PLoS One. 2018 Oct 11;13(10):e0205254. doi: 10.1371/journal.pone.0205254. PMID: 30307989; PMCID: PMC6181325.
[4]: Tenu JP, Lepoivre M, et,al. Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages. Nitric Oxide. 1999 Dec;3(6):427-38. doi: 10.1006/niox.1999.0255. PMID: 10637120.
[5]: Ding LY, Chen LM, et,al.Inhibition of arginase via jugular infusion of Nω-hydroxy-nor-l-arginine inhibits casein synthesis in lactating dairy cows. J Dairy Sci. 2018 Apr;101(4):3514-3523. doi: 10.3168/jds.2017-13178. Epub 2018 Feb 4. PMID: 29397169.
[6]: Wang MZ, Ding LY, et,al. Short communication: Arginase inhibition reduces the synthesis of casein in bovine mammary epithelial cells. J Dairy Sci. 2017 May;100(5):4128-4133. doi: 10.3168/jds.2016-11823. Epub 2017 Feb 23. PMID: 28237582.
[7]: RodrÍguez-GÓmez I, Manuel Moreno J, et,al. Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats. Am J Hypertens. 2015 Dec;28(12):1464-72. doi: 10.1093/ajh/hpv049. Epub 2015 Apr 23. PMID: 25907224.
nor-NOHA（醋酸盐）（α-氨基酸 N(omega) -Hydroxy-Nor-L-arginine）是一种有效且可逆的选择性精氨酸酶抑制剂,nor-NOHA（醋酸盐）的效力大约是 40 倍NOHA 抑制未受刺激的小鼠巨噬细胞催化 l-精氨酸水解为 l-鸟氨酸（nor-NOHA IC(50) 值 12 77777#177;5µM[4]。
nor-NOHA（醋酸盐）在缺氧条件下有效诱导表达 ARG2 的细胞凋亡,但在常氧条件下无效。与 nor-NOHA（醋酸盐）共同治疗克服了缺氧介导的对 BCR-ABL1 激酶抑制剂的耐药性。其抗白血病活性是独立的nor-NOHA (acetate) 在表达 ARG2 的缺氧细胞中具有显着但脱靶的抗白血病活性[3]. nor-NOHA (acetate) 可抑制增殖并诱导nor-NOHA（醋酸盐）抑制HepG2细胞的侵袭和迁移。这些数据表明nor-NOHA（醋酸盐）可以诱导细胞凋亡。 l 通过抑制Arg1[1]使HepG2细胞凋亡并抑制其侵袭和迁移能力。在BMEC（牛乳腺上皮细胞）中添加nor-NOHA（醋酸盐）可减少细胞增殖和酪蛋白合成。向 nor-NOHA（醋酸盐）中添加 Arg 会导致细胞增殖和酪蛋白合成,类似于单独使用 nor-NOHA（醋酸盐）。相比之下,与 nor-NOHA（乙酸盐）相比,在含有 nor-NOHA（乙酸盐）的培养基中添加 Orn 可增加酪蛋白的合成和细胞增殖[6]。
nor-NOHA（醋酸盐）治疗可以完全恢复健康大鼠对 Ach 的主动脉反应。这种有益作用是通过增加 NOS 活性和 EDHF 以及减少超氧阴离子产生来介导的,nor-NOHA（醋酸盐）抑制精氨酸酶活性IC50 小于 1 的主动脉 µm [2]。在中国荷斯坦奶牛中。测定了与精氨酸代谢、乳蛋白合成和 AA 转运蛋白表达相关的酶的活性。 nor-NOHA（醋酸盐）的输注降低了精氨酸酶的活性。此外,nor-NOHA（醋酸盐）的注入也减少了牛奶中蛋白质和脂肪的合成,但对牛奶产量没有影响[5]。大鼠甲状腺功能亢进症与表达和活性增加有关主动脉、心脏和肾脏中的精氨酸酶。用 nor-NOHA（乙酸盐）慢性精氨酸酶抑制可抑制甲状腺机能亢进症的特征性血液动力学表现,同时减少氧化应激[7]。
| Cas No. | 1140844-63-8 | SDF | |
| 别名 | Nω-hydroxy-nor-Arginine | ||
| 化学名 | 2S-amino-4-[[(hydroxyamino)iminomethyl]amino]-butanoic acid, diacetate | ||
| Canonical SMILES | N/C(N([H])CC[C@H](N)C(O)=O)=N\O.CC(O)=O.CC(O)=O | ||
| 分子式 | C5H12N4O3 • 2C2H4O2 | 分子量 | 296.3 |
| 溶解度 | ≤5mg/ml in DMSO;1mg/ml in dimethyl formamide | 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 | 3.375 mL | 16.8748 mL | 33.7496 mL |
| 5 mM | 0.675 mL | 3.375 mL | 6.7499 mL |
| 10 mM | 0.3375 mL | 1.6875 mL | 3.375 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。
PMA induces the differentiation of monocytes into immunosuppressive MDSCs
Clin Exp Immunol2021 Nov;206(2):216-225.PMID: 34453319DOI: 10.1111/cei.13657
The induction of immune tolerance without the use of immunosuppressive drugs is a crucial problem in organ transplantation. The use of myeloid-derived suppressor cells (MDSCs) as a cell-based adjuvant immunosuppressive therapy is a bright clinical prospect in organ transplantation. MDSCs with stable immunosuppressive activities can be used to treat immune-related diseases. In this study, macrophage colony-stimulating factor (M-CSF) was used to promote myeloid progenitor cell differentiation, and phorbol 12-myristate 13-acetate (PMA) was added to induce MDSCs at the later stage of induction in vitro. Cell phenotypes were detected by flow cytometry and mRNA was detected by real-time-polymerase chain reaction (RT-PCR). A mouse skin transplantation model was used to investigate the cell inhibitory function. The combination of PMA and M-CSF induced the differentiation of myeloid-derived monocytes into MDSCs. MDSCs were found to induce immune tolerance by inhibiting the proliferation and activation of T cells, promoting cytokine secretion and inducing T cell transformation to regulatory T cells (Treg ). PMA significantly up-regulated the expression of Arg-1 and the Arg-1 protein expression in MDSCs and arginase 1 (Arg-1) inhibitor nor-NOHA reversed the MDSC immunosuppressive activity, indicating the involvement of the Arg-1 pathway in MDSC-mediated immunosuppression. M-CSF + PMA-induced MDSCs also significantly prolonged the survival time of skin grafts in mice, showing that MDSCs exert immunosuppressive effects in vivo. We describe a novel scheme to induce immunosuppressive MDSCs in vitro. MDSCs induced by M-CSF with PMA showed stable immunosuppression. MDSCs induced by this protocol may benefit patients with organ transplantation through immune regulation.
Development of a new nano arginase HPLC capillary column for the fast screening of arginase inhibitors and evaluation of their binding affinity
J Chromatogr B Analyt Technol Biomed Life Sci2021 Jun 15;1175:122751.PMID: 33991957DOI: 10.1016/j.jchromb.2021.122751
A simple and rapid Nano LC method has been developed for the screening of arginase inhibitors. The method is based on the immobilization of biotinylated arginase on a neutravidin functionalized nano HPLC capillary column. The arginase immobilization step performed by frontal analysis is very fast and only takes a few minutes. The miniaturized capillary column of 170 nL (length 5 cm, internal diameter 75 ¦̭) significantly decreased the required amount of used enzyme (25 pmol). This was of significance importance when working with less available or expensive purified enzyme. Non-selective adsorption of the organic monolith matrix was reduced (<6%) and the arginase efficient yield was high (92%). The resultant affinity capillary columns showed excellent repeatability and long lifetime. The arginase reaction product was achieved within 60 s and the immobilized arginase retained 97% of the initial activity beyond 90 days. This novel approach can thus be used for the fast evaluation of recognition assay induced bya series of inhibitor molecules (caffeic acid phenylamide, chlorogenic acid, piceatannol, nor-NOHA acetate) and plant extracts.
Vasorelaxant effects of Crataegus pentagyna: Links with arginase inhibition and phenolic profile
J Ethnopharmacol2020 Apr 24;252:112559.PMID: 31935497DOI: 10.1016/j.jep.2020.112559
Ethnopharmacological relevance: Crataegus leaves, flowers and fruits have been traditionally used to improve blood circulation, numerous preclinical and clinical studies supporting the cardiovascular benefits of Crataegus preparations. In this respect, there is very limited data on Crataegus pentagyna; in addition, the chemical profile of this species is still incompletely elucidated.
Aim of the study: The objective of this study was to examine the cardiovascular benefits of Crataegus pentagyna Waldst. et Kit. ex Willd. (small-flowered black hawthorn, Rosaceae) extracts (leaf, flower and fruit ethyl acetate extracts) and the underlying mechanisms. We hypothesized that C. pentagyna extracts might exert vasodilatory effects and inhibit arginase activity due, in large part, to their polyphenolic constituents.
Materials and methods: C. pentagyna extracts induced-relaxation and the mechanisms involved were studied ex vivo in isolated aortic rings from Sprague-Dawley rats. The inhibitory effects on bovine liver arginase I were assessed by an in vitro assay. Metabolite profiling of C. pentagyna extracts was performed and the most endothelium- and nitric oxide synthase-dependent; flower extract additionally reduced Ca2+ entry and, to a lesser extent, Ca2+ release from the sarcoplasmic reticulum. C. pentagyna proved to be an important source of arginase inhibitors with potential benefits in endothelial dysfunction that remains to be explored.