JSH-23
(Synonyms: 4-甲基-N1-(3-苯基丙基)-1,2-苯二胺) 目录号 : GC11438
An inhibitor of NF-κB translocation
Cas No.:749886-87-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549 |
|
Preparation Method |
Cells were treated with different concentrations of NF-κB inhibitor JSH-23 (5, 10, 20, 30, 40, and 50 µM, respectively) for 24 h. |
|
Reaction Conditions |
5, 10, 20, 30, 40, and 50 µM for 24 hours |
|
Applications |
With the increase in JSH-23 concentration, the inhibition rate for cell viability was gradually increased, and significant differences existed when the JSH-23 concentration was greater than 20 µM. |
| Animal experiment [2]: | |
|
Animal models |
Male 12-week-old normotensive Wistar rats and Prague hereditary hypertriglyceridemic (HTG) rats |
|
Preparation Method |
Mice were given a total dose of either 20 mg/kg of JSH-23 (10 mg/kg 8 h prior to cisplatin injection and 5 mg/kg on days 1 and 2 after cisplatin injection) or a total dose of 40 mg/kg body weight of JSH-23 (20 mg/kg 8 h prior to cisplatin injection and 20 mg/kg on day 1 after cisplatin injection) or vehicle (DMSO). |
|
Dosage form |
Intraperitoneal injection, 5, 10, 20 mg/kg |
|
Applications |
JSH-23 (total dose of 40 mg/kg) resulted in a significant decrease in BUN, serum creatinine and serum NGAL. NGAL is an early diagnostic biomarker of cisplatin-induced AKI. JSH-23 had no effect on BUN and serum creatinine in vehicle-treated mice (Fig. 2). |
|
References: [1]: Huang L, Li F, Deng P, et al. MicroRNA-223 promotes tumor progression in lung cancer A549 cells via activation of the NF-κB signaling pathway[J]. Oncology research, 2016, 24(6): 405. | |
JSH-23, exhibited inhibitory effect on nuclear translocation and NF-κB transcriptional activity with an IC50 value of 7.1 μM in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 [1].
JSH-23 (1 μM) monotherapy significantly reduced the chemotactic sensitivity of the cells to SDF1. The co-treatment with cordycepin (10 μM) and JSH-23 (1 μM) significantly inhibited the expression of CXCR4 [2].
JSH-23 (1 and 3 mg/kg) treatment significantly reversed the nerve conduction and nerve blood flow deficits seen in diabetic animals [1]. Protein expression studies showed that nuclear translocation of p65/p50 subunit was inhibited by JSH-23 treatment in the sciatic nerve. The treatment also lowered the elevated IL-6, TNF-α, cyclo-oxygenase (COX-2) and inducible nitric oxide synthase (iNOS) levels/expression [1]. Mice were treated with JSH-23 (20 or 40 mg/kg) which directly affects NF-κB transcriptional activity. Kidney function, tubular injury (ATN, serum neutrophil gelatinase-associated lipocalin [NGAL], but not apoptosis) and myeloperoxidase (MPO) activity were significantly improved by JSH-23 (40 mg/kg) [3].
References:
[1]. Kumar A, Negi G, Sharma S S. JSH?\23 targets nuclear factor?\kappa B and reverses various deficits in experimental diabetic neuropathy: effect on neuroinflammation and antioxidant defence[J]. Diabetes, Obesity and Metabolism, 2011, 13(8): 750-758.
[2]. Guo Z, Chen W, Dai G, et al. Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4[J]. International journal of molecular medicine, 2020, 45(1): 141-150.
[3]. Ozkok A, Ravichandran K, Wang Q, et al. NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI)[J]. Toxicology letters, 2016, 240(1): 105-113.
JSH-23 对核转位和 NF-κB 转录活性具有抑制作用，在脂多糖 (LPS) 刺激的巨噬细胞中 IC50 值为 7.1 μM RAW 264.7 [1]。
\nJSH-23 (1 μM) 单一疗法显着降低了细胞对 SDF1 的趋化敏感性。虫草素（10 μM）和JSH-23（1 μM）联合处理显着抑制了CXCR4[2]的表达。
JSH-23（1 和 3 mg/kg）治疗可显着逆转糖尿病动物中观察到的神经传导和神经血流缺陷[1]。蛋白质表达研究表明，坐骨神经中的 JSH-23 处理可抑制 p65/p50 亚基的核转位。该治疗还降低了升高的 IL-6、TNF-α、环氧合酶 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 水平/表达 [1]。用直接影响 NF-κB 转录活性的 JSH-23（20 或 40 mg/kg）处理小鼠。 JSH-23 (40 mg/kg) 显着改善肾功能、肾小管损伤（ATN、血清中性粒细胞明胶酶相关脂质运载蛋白 [NGAL]，但不影响细胞凋亡）和髓过氧化物酶 (MPO) 活性[3].
| Cas No. | 749886-87-1 | SDF | |
| 别名 | 4-甲基-N1-(3-苯基丙基)-1,2-苯二胺 | ||
| 化学名 | 4-methyl-1-N-(3-phenylpropyl)benzene-1,2-diamine | ||
| Canonical SMILES | CC1=CC(=C(C=C1)NCCCC2=CC=CC=C2)N | ||
| 分子式 | C16H20N2 | 分子量 | 240.34 |
| 溶解度 | ≥ 24mg/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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 4.1608 mL | 20.8039 mL | 41.6077 mL |
| 5 mM | 0.8322 mL | 4.1608 mL | 8.3215 mL |
| 10 mM | 0.4161 mL | 2.0804 mL | 4.1608 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。
The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis
Front Pharmacol2021 Sep 9;12:734774.PMID: 34566656DOI: 10.3389/fphar.2021.734774
Inflammatory osteolysis is a pathological skeletal disease associated with not only the production of inflammatory cytokines but also local oxidative status. Excessive reactive oxygen species (ROS) promote bone resorption by osteoclasts and induce the apoptosis of osteoblasts. In consideration of the lack of effective preventive or treatments options against osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. In our study, we found that a novel antioxidant compound, JSH-23, plays a role in restoring bone homeostasis by scavenging intracellular ROS during both osteoclastogenesis and osteoblastogenesis. Mechanically, JSH-23 suppressed RANKL-induced osteoclastogenesis, bone resorption and the expression of specific genes (including NFATc1, c-Fos, TRAP, CTSK and DC-STAMP) via inhibition of the NF-κB signaling pathway. Meanwhile, JSH-23 suppressed RANKL-induced ROS generation via the TRAF6/Rac1/NOX1 pathway and the enhanced expression of Nrf2/HO-1. In addition, JSH-23 attenuated H2O2-induced apoptosis and mineralization reduction in osteoblasts by reducing ROS production and enhancing Nrf2/HO-1 expression. Our in vivo results further revealed that JSH-23 exerts its protective effects on bone mass through its antioxidant activity. In conclusion, our results show that the application of JSH-23 might be a novel and plausible strategy for the treatment of osteolysis-related disease.
NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling
Cell Death Dis2019 Dec 2;10(12):906.PMID: 31787755DOI: 10.1038/s41419-019-2157-1
Inflammatory bowel disease (IBD) is one of the most common diseases in the gastrointestinal tract related to aberrant inflammation. Pyroptosis, which is characterized by inflammasome formation, the activation of caspase-1, and the separation of the N- and C-terminals of GSDMD, might be related to IBD pathogenesis. NEK7 is an important component of the NLRP3 inflammasome in macrophages. We attempted to investigate the mechanism of NEK7 interacting with NLRP3 to modulate the pyroptosis in IBD. NEK7 mRNA and protein expression and pyroptosis-associated factors, including Caspase-1 (p45, p20), NLRP3, and GSDMD, were upregulated in IBD tissues. NEK7 knockdown abolish ATP + LPS-induced pyroptosis in vitro and improved DSS-induced chronic colitis in vivo. NEK7 interacted with NLRP3, as revealed by Co-IP and GST pull-down assays, to exert its effects. Moreover, short-term LPS treatment alone induced no significant changes in NEK7 protein level. TLR4/NF-κB signaling in MODE-K cells could be activated by LPS treatment. LPS-induced NEK7 upregulation could be significantly reversed by JSH-23, an inhibitor of p65. Furthermore, LUC and ChIP assays revealed that RELA might activate the transcription of NEK7 via targeting its promoter region. LPS-induced TLR4/NF-κB activation causes an increase in NEK7 expression by RELA binding NEK7 promoter region. In conclusion, NEK7 interacts with NLRP3 to modulate NLRP3 inflammasome activation, therefore modulating the pyroptosis in MODE-K cells and DSS-induced chronic colitis in mice. We provide a novel mechanism of NEK7-NLRP3 interaction affecting IBD via pyroptosis.
JSH-23 prevents depressive-like behaviors in mice subjected to chronic mild stress: Effects on inflammation and antioxidant defense in the hippocampus
Pharmacol Biochem Behav2018 Jun;169:59-66.PMID: 29684396DOI: 10.1016/j.pbb.2018.04.005
Nuclear factor-kappa B (NF-κB), which is reported to play an important role in the pathogenesis of depression, also has a central role in the genesis and progression of inflammation. Here, we have targeted the nuclear translocation of NF-κB using 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) to elucidate its role in depression. We investigated the antidepressant-like effects of JSH-23 in the chronic mild stress (CMS) mouse model, which is a valid, reasonably reliable, and useful model of depression. The antidepressant-like effects of JSH-23 were evaluated using the sucrose preference test (SPT) and the forced swimming test (FST). We also assessed inflammatory markers [interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)] and components of antioxidant defense [superoxide dismutase (SOD) and nuclear factor erythroid-2-related factor 2 (Nrf 2)] in the hippocampus. Fluoxetine, a classical antidepressant, was used in this study as a positive control. Administration of JSH-23 significantly prevented the decreased sucrose preference in the SPT and prevented the increased immobility time in the FST caused by CMS, but had no effect on locomotor activity. Expression of NF-κB p65 protein in the hippocampus was decreased, and elevated levels of IL-6 and TNF-α were reduced, after JSH-23 administration. In addition to its anti-inflammatory effect, JSH-23 treatment increased the expression of SOD and Nrf 2 in the hippocampus, suggesting that it strengthens antioxidant defense. The current study demonstrated that inhibiting the NF-κB signaling cascade using JSH-23 prevented depressive-like behaviors by decreasing inflammation and improving antioxidant defense in the hippocampus. We concluded that NF-κB activation plays an important role in the pathophysiology of depression and that targeting NF-κB signaling may provide a novel and effective therapy for depression. Additional preclinical studies and clinical trials are, however, needed to further elucidate the effects of this therapeutic strategy.
Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion
Small2022 Apr;18(13):e2104112.PMID: 34816589DOI: 10.1002/smll.202104112
Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.
ATG5-mediated autophagy suppresses NF-κB signaling to limit epithelial inflammatory response to kidney injury
Cell Death Dis2019 Mar 15;10(4):253.PMID: 30874544DOI: 10.1038/s41419-019-1483-7
G2/M-arrested proximal tubular epithelial cells (TECs) after renal injury are linked to increased cytokines production. ATG5-mediated autophagy in proximal TECs has recently been shown to protect against G2/M cell cycle arrest and renal fibrosis. However, the impacts of autophagy in regulating inflammatorily response mounted by injured TECs remains largely unknown. In the present study, we investigated whether ATG5 acts as an innate immune suppressor in proximal TECs during kidney injury. Using the unilateral ureteric obstruction model in proximal tubule-specific autophagy-deficient mice, we demonstrated that ablation of epithelial ATG5 genes markedly impaired autophagy, resulting in enhanced nuclear factor κB (NF-κB) activation, macrophage and lymphocyte infiltration, and proinflammatory cytokines production in obstructed kidneys, as compared with wild-type mice. Following stimulation with angiotensin II (Ang II), siRNA silencing of ATG5 in cultured HK-2 cells or ATG5-deficient primary proximal TECs produced more cytokines, including IL-1β, IL-6, and TNF-α than did their control cells. Overexpressed ATG5, but not the autophagy-incompetent ATG5 mutant K130R in HK-2 cells, rendered resistant to Ang II-induced inflammatory response. Immunofluorescence assay indicated that ATG5 and p65 colocalized in the nucleus and cytoplasm, and their interaction was verified in immunoprecipitation assay from HEK-293T cell extracts. Genetic downregulation of endogenous ATG5 increased Ang II-induced phosphorylation and nuclear translocation of p65 and transcriptional activity of NF-κB, whereas the overexpressed ATG5, rather than ATG5 mutant K130R, hampered activation of NF-κB signaling, suggest an autophagy-dependent anti-inflammatory effect of ATG5. Further, pharmacological manipulation of autophagy yielded similar results both in vivo and in vitro. Additionally, JSH-23, a specific inhibitor of NF-κB nuclear translocation, rescued Ang II-driven IL-1β production in ATG5 siRNA-treated cells and decreased the proportion of cells in G2/M phase. In conclusion, ATG5-mediated autophagy in tubules targets NF-κB signaling to protect against renal inflammation.