FG-4592 (ASP1517)
(Synonyms: 罗沙司他,Roxadustat) 目录号 : GC13139
FG-4592 作为一种口服生物可利用的缺氧诱导因子 (HIF) 脯氨酰羟化酶抑制剂，可通过 HIF 介导的转录促进协调性红细胞生成。
Cas No.:808118-40-3
Sample solution is provided at 25 µL, 10mM.
FG-4592, as an oral bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, can promote coordinated erythropoiesis through HIF-mediated transcription. FG-4592 was well tolerated and corrected anemia in incident HD and PD patients.[1]
In vitro, treated with 10 μM or 50 μM FG-4592 in Primary Hippocampal Neurons, FG-4592 dose-dependently increased protein levels of HIF-1, and its target genes EPO and VEGF, as well as BDNF and PSD95.[2] In vitro experiment it exhibited that treatment with 2, 10, and 20 μM FG-4592 dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway.[3] In HK-2 cells, treatment with 15?μM FG-4592 the injury induced by hypoxia remarkably ameliorated.[5]
In vivo experiment it shown that treatment with 20 mg/kg/day FG-4592 intraperitoneally in Rat significantly affected body weight gain. In vivo efficacy it indicated that the high dose FG-4592 (20 mg/kg/day) could effectively reverse CUMS-induced depression-like behaviors. [2] In vivo, mice were treated with 10 mg/kg FG-4592 intraperitoneally exhibited an improved renal function, compared with those without FG-4592 by biochemical and histological parameters.[4] In C57BL/6 mice, treatment with 25.0 mg/kg FG-4592 intraperitoneally 24 and 2 h before irradiation, and then followed by total body irradiation of 8.5 Gy or local abdominal irradiation of 25.0 Gy could dramatically improve the survival rate of mice after IR.[6]
References:
[1]Besarab A, Chernyavskaya E, Motylev I, Shutov E, Kumbar LM, Gurevich K, Chan DT, Leong R, et al. Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. J Am Soc Nephrol. 2016 Apr;27(4):1225-33.?
[2]Li G, et al. FG-4592 Improves Depressive-Like Behaviors through HIF-1-Mediated Neurogenesis and Synapse Plasticity in Rats. Neurotherapeutics. 2020 Apr;17(2):664-675.?
[3]Yang DG, et al. Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway. Acta Pharmacol Sin. 2022 Aug 10.?
[4]Li X, et al. Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway. Oxid Med Cell Longev. 2020 Jan 20;2020:6286984.
[5]Miao AF, et al. Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation. Ren Fail. 2021 Dec;43(1):803-810.
[6]Feng Z, et al. FG-4592 protects the intestine from irradiation-induced injury by targeting the TLR4 signaling pathway. Stem Cell Res Ther. 2022 Jun 21;13(1):271.
FG-4592 作为一种口服生物可利用的缺氧诱导因子 (HIF) 脯氨酰羟化酶抑制剂,可通过 HIF 介导的转录促进协调性红细胞生成。 FG-4592 在新发 HD 和 PD 患者中具有良好的耐受性并纠正了贫血。[1]
在体外,用 10 μM 或 50 μM FG-4592 处理原代海马神经元,FG-4592 以剂量依赖性方式增加 HIF-1 及其靶基因 EPO 和 VEGF,以及 BDNF 和 PSD95 的蛋白质水平。 [2] 体外实验表明,2、10 和 20 μM FG-4592 剂量依赖性地减少 LPS 刺激的 BV-2 细胞（一种小鼠小胶质细胞系）中的 ROS 生成和炎症, 通过抑制 HIF-1α/NF-κB 通路。[3] 在 HK-2 细胞中,用 15μM FG-4592 处理缺氧诱导的损伤显着改善。[5]
体内实验表明,用 20 毫克/千克/天的 FG-4592 对大鼠进行腹膜内注射处理会显着影响体重增加。体内功效表明高剂量 FG-4592（20 mg/kg/天）可以有效逆转 CUMS 诱导的抑郁样行为。 [2] 在体内,与未使用 FG-4592 的小鼠相比,腹膜内注射 10 mg/kg FG-4592 的小鼠在生化和组织学参数方面表现出改善的肾功能。[4] 在 C57BL/6 小鼠中,在照射前 24 小时和 2 小时腹腔注射 25.0 mg/kg FG-4592,然后进行 8.5 Gy 的全身照射或 25.0 Gy 的局部腹部照射可以显着提高存活率IR 后的小鼠。[6]
| Cell experiment [1]: | |
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Cell lines |
Primary culture of hippocampal neurons |
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Preparation Method |
Hippocampal primary neurons were treated with 50 μM and 10 μM FG-4592 for 72 h, starting from the second day in vitro. Microtubule-associated protein 2 (MAP2) staining and Western blotting were performed after cell collection. |
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Reaction Conditions |
50 μM and 10 μM, 72h |
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Applications |
FG-4592 promoted dendritic growth of primary hippocampal neurons in vitro. |
| Animal experiment [2]: | |
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Animal models |
Wild-type C57BL/6 mice (10–12 weeks old, weighing 25–28 g) |
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Preparation Method |
The FG-4592 was dissolved in DMSO at the concentration of 50 mg/ml and further diluted in PBS to 1 mg/ml. The mice were pretreated with FG-4592 for 48 h in FG-4592+Doxorubicin group at a dose of 10 mg/kg/day before Doxorubicin treatment. |
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Dosage form |
10 mg/kg/day;intraperitoneal injection |
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Applications |
FG-4592 rescued the reduction of LVEF and LVFS induced by Doxorubicin. FG-4592 obviously attenuated Doxorubicin-induced acute cardiac dysfunction and cardiomyocyte injury. |
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References: [1]. Li G, et al. FG-4592 Improves Depressive-Like Behaviors through HIF-1-Mediated Neurogenesis and Synapse Plasticity in Rats. Neurotherapeutics. 2020 Apr;17(2):664-675. [2]. Long G, et al. Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways. Front Pharmacol. 2020 Aug 5;11:1191. |
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| Cas No. | 808118-40-3 | SDF | |
| 别名 | 罗沙司他,Roxadustat | ||
| 化学名 | 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid | ||
| Canonical SMILES | CC1=NC(=C(C2=C1C=C(C=C2)OC3=CC=CC=C3)O)C(=O)NCC(=O)O | ||
| 分子式 | C19H16N2O5 | 分子量 | 352.34 |
| 溶解度 | ≥ 17.62 mg/mL in DMSO, ≥ 2.9 mg/mL in EtOH with ultrasonic and warming | 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 | 2.8382 mL | 14.1908 mL | 28.3817 mL |
| 5 mM | 0.5676 mL | 2.8382 mL | 5.6763 mL |
| 10 mM | 0.2838 mL | 1.4191 mL | 2.8382 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。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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