AGK 2
(Synonyms: 2-氰基-3-[5-(2,5-二氯苯基)-2-呋喃基]-N-5-喹啉基-2-丙烯酰胺) 目录号 : GC17881
AGK2是一种选择性的SIRT2 抑制剂,IC50为3.5 µM。
Cas No.:304896-28-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
RBL-2H3 cell |
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Preparation method |
Cells were incubated with AGK2, total β-glucosamine activity was measured. |
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Reaction Conditions |
0.01–20 μM;24 h |
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Applications |
AGK2 treatment reduced high levels of β-hexosaminidase and histamine in RBL-2H3 cells. |
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Animal experiment [2]: |
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Animal models |
Male C57BL/6 J mice (6–7 weeks) |
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Preparation method |
Mice were divided into four groups: namely, control, LPS, AGK2 plus LPS, and AGK2 group. The LPS group was administrated by intraperitoneal injection with LPS (10 mg/kg). The dosage of AGK2 was 1 μmol/mouse. AGK2 (25 mg) was dissolved in DMSO and formed 10 mM mother liquor. Then, the solution was diluted in normal saline (NS) and formed final concentration of AGK2 (400 μM, 4% DMSO). For AGK2 + LPS group and AGK2 group, 2.5 ml AGK2 (400 μM) was injected into abdominal cavities of each mouse. AGK2 was given in AGK2 plus LPS group before LPS administration 2 h. The same volume of 4% DMSO solution was injected in control group as well. All mice were sacrificed, and the brain tissues were harvested at 24 h after LPS treatment. |
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Dosage form |
1 μmol/mouse; i.p;26h |
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Applications |
AGK2 suppressed the expression of inflammatory cytokines after LPS treatment in mice brain. |
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References: [1]. Kim YY, Hur G, et,al. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway. Pharmacol Res. 2020 Sep;159:105027. doi: 10.1016/j.phrs.2020.105027. Epub 2020 Jun 18. PMID: 32565308. [2]. Jiao F, Wang Y, et,al. AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1. J Neuroimmune Pharmacol. 2020 Jun;15(2):196-208. doi: 10.1007/s11481-019-09890-x. Epub 2019 Nov 30. PMID: 31786712. |
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AGK2 is a selective SIRT2 inhibitor, with an IC50 of 3.5 µM. AGK2 inhibits SIRT1 and SIRT3 with IC50 of 30 and 91 µM, respectively[1,2].
AGK2(0.01-20 µM;24 h) inhibits mast cell degranulation in vitro, AGK2 treatment reduced high levels of β-hexosaminidase and histamine in RBL-2H3 cells[3]. AGK2(1-5 µM;24 h) suppress cell growth and migration by inhibiting HSF1 protein stability in HeLa cells[4]. Sirtuin 2 (SIRT2) inhibition by AGK2 significantly enhances the BCG vaccine efficacy during primary infection and TB recurrence through enhanced stem cell memory (TSCM) responses[5].
AGK2(1 µmol/mouse;i.p;26h) could inhibit the activation of BV2 microglia and expression of iNOS and SIRT2 in LPS treated mice brain tissue[6]. AGK2 (1µmol/mouse;i.p;26h)pretreatment also reduced the levels of pro-inflammatory cytokines in acute liver failure (ALF) liver tissues. AGK2 improved the thioacetamide (TAA)-induced survival rate[7]. AGK2(82 mg/kg;i.p;7days) treatment inhibited serum HBV DNA, HBeAg and HBsAg levels as well as hepatic HBV DNA, RNA and HBc in the HBV transgenic mice[8].
References:
[1]. Tatum PR, Sawada H, et,al. Identification of novel SIRT2-selective inhibitors using a click chemistry approach. Bioorg Med Chem Lett. 2014 Apr 15;24(8):1871-4. doi: 10.1016/j.bmcl.2014.03.026. Epub 2014 Mar 20. PMID: 24675380.
[2]. Outeiro TF, Kontopoulos E, et,al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007 Jul 27;317(5837):516-9. doi: 10.1126/science.1143780. Epub 2007 Jun 21. PMID: 17588900.
[3]. Kim YY, Hur G, et,al. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway. Pharmacol Res. 2020 Sep;159:105027. doi: 10.1016/j.phrs.2020.105027. Epub 2020 Jun 18. PMID: 32565308.
[4]. Kim HW, Kim SA, et,al. Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability. Oncol Rep. 2016 Jan;35(1):235-42. doi: 10.3892/or.2015.4381. Epub 2015 Nov 2. PMID: 26530275.
[5]. Bhaskar A, Pahuja I, et,al. SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis. iScience. 2023 Apr 10;26(5):106644. doi: 10.1016/j.isci.2023.106644. PMID: 37192966; PMCID: PMC10182326.
[6]. Jiao F, Wang Y, et,al. AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1. J Neuroimmune Pharmacol. 2020 Jun;15(2):196-208. doi: 10.1007/s11481-019-09890-x. Epub 2019 Nov 30. PMID: 31786712.
[7]. Jiao FZ, Wang Y, et,al. Protective role of AGK2 on thioacetamide-induced acute liver failure in mice. Life Sci. 2019 Aug 1;230:68-75. doi: 10.1016/j.lfs.2019.05.061. Epub 2019 May 23. PMID: 31129140.
[8]. Yu HB, Jiang H, et,al. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int J Med Sci. 2018 Sep 7;15(12):1356-1364. doi: 10.7150/ijms.26125. PMID: 30275764; PMCID: PMC6158674.
AGK2是一种选择性的SIRT2 抑制剂,IC50为3.5 µM。AGK2 抑制SIRT1 和SIRT3 的IC50 分别为30和91 µM [1,2]。
AGK2 (0.01-20 µM；24h)在体外抑制肥大细胞脱颗粒作用,AGK2 处理能够减少RBL-2H3 细胞中β-己糖苷酶和组胺高水平的表达[3]。AGK2 (1-5 µM；24h) 通过抑制HeLa 细胞中HSF1 蛋白的稳定性,抑制细胞的生长和迁移[4]。AGK2 对SIRT2 抑制可通过增强干细胞记忆(TSCM)反应,显著增强卡介苗(BCG)的主要感染和结核病复发的疗效[5]。
AGK2 (1 µmol/mice；i.p；26h) 能够抑制LPS 处理小鼠脑组织中BV2 微胶质细胞的活化和iNOS、SIRT2 的表达[6]。AGK2 (1µmol/mice；i.p；26h) 预处理可以降低ALF 肝脏组织中的促炎性细胞因子水平。AGK2 也能改善TAA 引起的生存率[7]。AGK2 (82 mg/kg；i.p；7days) 处理可以抑制HBV 转基因小鼠血清中的HBV DNA、HBeAg 和HBsAg 水平,以及肝脏中的HBV DNA、RNA 和HBc 的表达[8]。
| Cas No. | 304896-28-4 | SDF | |
| 别名 | 2-氰基-3-[5-(2,5-二氯苯基)-2-呋喃基]-N-5-喹啉基-2-丙烯酰胺 | ||
| 化学名 | (E)-2-cyano-3-(5-(2,5-dichlorophenyl)furan-2-yl)-N-(quinolin-5-yl)acrylamide | ||
| Canonical SMILES | ClC(C(C1=CC=C(/C=C(C#N)/C(NC2=C3C(N=CC=C3)=CC=C2)=O)O1)=C4)=CC=C4Cl | ||
| 分子式 | C23H13Cl2N3O2 | 分子量 | 434.27 |
| 溶解度 | ≥ 9.3mg/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 | 2.3027 mL | 11.5136 mL | 23.0271 mL |
| 5 mM | 0.4605 mL | 2.3027 mL | 4.6054 mL |
| 10 mM | 0.2303 mL | 1.1514 mL | 2.3027 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。