Feprazone
(Synonyms: 非普拉宗,DA2370; Prenazone; Zepelin) 目录号 : GC40565
A COX-2 inhibitor
Cas No.:30748-29-9
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Feprazone is a non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor that is 10-fold selective for COX-2 over COX-1. It reduces LPS-induced prostaglandin E2 production in bovine arterial endothelial cells (IC50 = 1 μM). Oral administration of feprazone (25-100 mg/kg) reduces vascular permeability, edema, and nociception in a rat model of adjuvant-induced arthritis.
| Cas No. | 30748-29-9 | SDF | |
| 别名 | 非普拉宗,DA2370; Prenazone; Zepelin | ||
| Canonical SMILES | O=C1C(C/C=C(C)/C)C(N(C2=CC=CC=C2)N1C3=CC=CC=C3)=O | ||
| 分子式 | C20H20N2O2 | 分子量 | 320.4 |
| 溶解度 | DMF: 25 mg/mL,DMSO: 25 mg/mL,Ethanol: 50 mg/mL,PBS (pH 7.2): 0.5 mg/mL,Water: 1 mg/mL | 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 | 3.1211 mL | 15.6055 mL | 31.211 mL |
| 5 mM | 0.6242 mL | 3.1211 mL | 6.2422 mL |
| 10 mM | 0.3121 mL | 1.5605 mL | 3.1211 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。
Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes
ACS Omega 2021 Mar 31;6(14):9442-9448.PMID:33869924DOI:10.1021/acsomega.0c06066.
The proinflammatory cytokine interleukin-1 β (IL-1β)-mediated cellular senescence in chondrocytes is involved in the development and pathological progression of osteoarthritis (OA). Feprazone, a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX) inhibitor, is widely used in clinics. This study aims to investigate whether Feprazone has a protective effect against IL-1β-induced cellular senescence in human chondrocytes. In this study, C-28/I2 chondrocytes were stimulated with IL-1β (10 ng/mL) in the presence or absence of Feprazone (10 and 20 μM). Cellular senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) staining. The cell cycle was examined using flow cytometry. Gene and protein expressions were determined with real-time polymerase chain reaction (PCR) and western blot analysis. We found that treatment with Feprazone ameliorated IL-1β-induced increase in cellular senescence. Feprazone increased telomerase activity and prevented cell cycle arrest in the G0/G1 phase. We also found that Feprazone reduced the expressions of plasminogen activator inhibitor-1 (PAI-1) and p21, two important regulators of cellular senescence. Additionally, treatment with Feprazone reduced the expressions of matrix metalloprotein (MMP-13) and a disintegrin-like and metalloproteinase with thrombospondin type-1 motif-5 (ADAMTS-5). Interestingly, Feprazone prevented the activation of nuclear factor kappa-B (NF-κB) by preventing nuclear translocation of NF-κB p65 and the luciferase activity of the NF-κB promoter. The results also show that Feprazone increased nuclear levels of nuclear factor erythroid 2-related factor-2 (Nrf2) and reduced the production of reactive oxygen species (ROS). Importantly, silencing of Nrf2 abolished the protective effects of Feprazone against IL-1β-induced NF-κB activation and cellular senescence. These findings shed light on the potential use of Feprazone in the treatment of OA based on a novel mechanism.
Feprazone Ameliorates TNF-α-Induced Loss of Aggrecan via Inhibition of the SOX-4/ADAMTS-5 Signaling Pathway
ACS Omega 2021 Mar 12;6(11):7638-7645.PMID:33778274DOI:10.1021/acsomega.0c06212.
Background: Arthritis is a cartilage degenerative disease that is mainly induced by the degradation of the cartilage extracellular matrix (ECM), which is found to be regulated by the expression level of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMT-5), an enzyme degrading Aggrecans in the ECM. Feprazone is a classic nonsteroidal anti-inflammatory drug with promising efficacy in arthritis. The present study aims to investigate the protective effect of Feprazone on the degraded Aggrecan in the human chondrocytes induced with tumor necrosis factor-α (TNF-α) and to clarify the underlying mechanism. Methods: To investigate the effect of Feprazone, the CHON-001 chondrocytes were stimulated with TNF-α (10 ng/mL) in the presence or absence of Feprazone (3, 6 μM) for 24 h. Mitochondrial membrane potential was evaluated using the Rhodamine 123 assay. The gene expressions of interleukin-1β (IL-1β), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and ADAMTS-5 in the treated chondrocytes were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the protein levels of these targets were determined using enzyme-linked immunosorbent assay (ELISA). SOX-4 was knocked down by transfecting the siRNA into the chondrocytes. Western blot analysis was utilized to evaluate the expression levels of SOX-4, Aggrecan, and protein kinase C (PKCα). Results: First, the reduced mitochondrial membrane potential (ΔΨm) and secretion of proinflammatory factors (IL-1β, IL-8, and MCP-1) induced by TNF-α were significantly reversed by treatment with Feprazone. Second, the expression of Aggrecan was significantly decreased by stimulation with TNF-α via upregulation of ADAMTS-5 but was dramatically reversed by the introduction of Feprazone. Third, we found that TNF-α elevated the expression of ADAMTS-5 by upregulating SOX-4, which was observed to be related to the activation of PKCα. Lastly, the elevated expression of SOX-4 induced by TNF-α was significantly reversed by Feprazone. Conclusions: Feprazone might ameliorate TNF-α-induced loss of Aggrecan via the inhibition of the SOX-4/ADAMTS-5 signaling pathway.
Feprazone Displays Antiadipogenesis and Antiobesity Capacities in in Vitro 3 T3-L1 Cells and in Vivo Mice
ACS Omega 2021 Mar 7;6(10):6674-6680.PMID:33748580DOI:10.1021/acsomega.0c05470.
Background and purpose: Excessive lipid accumulation in adipose tissues and deregulation of adipogenesis-induced obesity affect millions of people worldwide. Feprazone, a nonsteroidal anti-inflammatory drug, has a wide clinical use. However, it is unknown whether Feprazone possesses an antiadipogenic ability. The aim of this study is to investigate whether Feprazone possesses an antiadipogenic ability in 3 T3-L1 cells and an antiobesity capacity in mouse models. Methods: An MTT assay was used to determine the optimized incubation concentrations of Feprazone in 3 T3-L1 cells. The lipid accumulation was evaluated using Oil Red O staining. The concentrations of triglyceride and glycerol release were detected to check the lipolysis during 3 T3-L1 adipogenesis. A quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of sterol regulatory element-binding protein-1C (SREBP-1C) and fatty acid binding protein 4 (FABP4) in treated cells. The expressions of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein α (C/EBP-α), adipose triglyceride lipase (ATGL), and aquaporin-7 (AQP-7) were detected using qRT-PCR and Western blot analysis. After the high-fat diet (HFD) mice were treated with Feprazone, the pathological state of adipocyte tissues was evaluated using HE staining. The adipocyte size, visceral adipocyte tissue weight, and bodyweights were recorded. Results: According to the proliferation result, 30 and 60 μM Feprazone were used as the optimized concentrations of Feprazone. In the in vitro study, lipid accumulation, elevated production of triglycerides, the release of glycerol, upregulated SREBP-1C, FABP4, PPAR-γ, and C/EBP-α and downregulated ATGL and AQP-7 in the 3 T3-L1 adipocytes induced by the adipocyte differentiation cocktail medium were significantly reversed by treatment with Feprazone. In the in vivo experiment, we found that the increased adipocyte size, visceral adipocyte tissue weight, and body weights induced by HFD feeding in mice were significantly suppressed by the administration of Feprazone. Conclusion: Feprazone might display anti-adipogenic and antiobesity capacities in in vitro 3 T3-L1 cells and in vivo mice.
Feprazone Prevents Free Fatty Acid (FFA)-Induced Endothelial Inflammation by Mitigating the Activation of the TLR4/MyD88/NF-κB Pathway
ACS Omega 2021 Feb 9;6(7):4850-4856.PMID:33644593DOI:10.1021/acsomega.0c05826.
Increased levels of free fatty acid (FFA)-induced endothelial dysfunction play an important role in the initiation and development of atherosclerosis. Feprazone is a nonsteroidal anti-inflammatory compound. However, the beneficial effects of Feprazone on FFA-induced endothelial dysfunction have not been reported before. In the current study, we found that treatment with Feprazone ameliorated FFA-induced cell death of human aortic endothelial cells (HAECs) by restoring cell viability and reducing the release of lactate dehydrogenase (LDH). Importantly, we found that treatment with Feprazone ameliorated FFA-induced oxidative stress by reducing the production of mitochondrial reactive oxygen species (ROS). In addition, Feprazone prevented FFA-induced expression and secretion of proinflammatory cytokines and chemokines, such as chemokine ligand 5 (CCL5), interleukin-6 (IL-6), and interleukin-8 (IL-8). We also found that Feprazone decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Interestingly, we found that Feprazone reduced the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). Our results also demonstrate that Feprazone prevented FFA-induced activation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. These findings suggest that Feprazone might serve as a potential agent for the treatment of atherosclerosis by improving the endothelial function.
Correction to "Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes"
ACS Omega 2022 Feb 15;7(8):7430.PMID:35252733DOI:10.1021/acsomega.2c00749.
[This corrects the article DOI: 10.1021/acsomega.0c06066.].