Halofuginone (RU-19110),Febrifugine 的衍生物,是一种竞争性的脯氨酰-tRNA 合成酶 (prolyl-tRNA synthetase) 抑制剂,Ki为 18.3 nM。Halofuginone 是 I 型胶原 (type-I collagen) 合成的特异性抑制剂,并通过抑制TGF-β活性可减轻骨关节炎。Halofuginone 也是一种有效的肺血管扩张剂,可激活Kv通道并阻断电压门控、受体操作和存储操作的Ca2+channels通道。Halofuginone 具有抗疟疾、抗炎、抗癌、抗纤维化作用。
生物活性 | Halofuginone (RU-19110), a Febrifugine derivative, is a competitiveprolyl-tRNA synthetaseinhibitor with aKiof 18.3 nM[1][2]. Halofuginone is a specific inhibitor oftype-I collagensynthesis and attenuates osteoarthritis (OA) by inhibition ofTGF-βactivity[3][4]. Halofuginone is also a potent pulmonary vasodilator by activatingKv channelsand blocking voltage-gated, receptor-operated and store-operatedCa2+channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects[5]. |
IC50& Target | Ki: 18.3±0.5 nM (prolyl-tRNA synthetase)[2] |
体外研究 (In Vitro) | Halofuginone competitively inhibits prolyl-tRNA synthetase by occupying both the prolineand tRNA-binding pockets of prolyl-tRNA synthetase[1]. The IC50s of Halofuginone (1, 10, 100, 1000, 10000 nM; 48 hours) are 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. The IC50s of Halofuginone (1, 10, 100, 1000 nM; 24 hours) for NRF2 protein are 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. The IC50of Halofuginone for global protein synthesis is 22.6 and 45.7 nM in KYSE70 and A549 cells, respectively[1]. Halofuginone increases voltage-gated K+(Kv) currents in pulmonary artery smooth muscle cells (PASMC) and K+currents through KCNA5 channels in HEK cells transfected with KCNA5 gene. Halofuginone (0.03-1μM) inhibits receptor-operated Ca2+entry (ROCE) in HEK cells transfected with calcium-sensing receptor gene and attenuated store-operated (SOCE) Ca2+entry in PASMC[5].
Cell Viability Assay[1] Cell Line: | KYSE70 cells from human oesophageal cancer harbouring a mutation in theNRF2gene and A549 cells harbouring theKEAP1gene mutation | Concentration: | 1, 10, 100, 1000, 10000 nM | Incubation Time: | 48 hours | Result: | The IC50s were 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. |
Western Blot Analysis[1] Cell Line: | KYSE70 cells from human oesophageal cancer harbouring a mutation in theNRF2gene and A549 cells harbouring theKEAP1gene mutation. | Concentration: | 1, 10, 100, 1000 nM | Incubation Time: | 24 hours | Result: | The IC50s for NRF2 protein were 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. |
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体内研究 (In Vivo) | Halofuginone (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration (0.2 or 0.5 mg/kg) has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage[3]. Halofuginone (0.25 mg/kg; intraperitoneally injected; every day; 16 days) decreases NRF2 protein levels in tumors. While the tumor volumes do not change substantially between treatments with the vehicle, Halofuginone (0.25 mg/kg, intraperitoneally injected, every day) or cisplatin alone. Combined treatment with Halofuginone and Cisplatin significantly suppresses the tumor volume compared to treatment with Halofuginone or cisplatin alone[1]. Intraperitoneal administration of Halofuginone (0.3mg/kg, for 2 weeks) partially reverses the established pulmonary hypertension in mice[5].
Animal Model: | 3-month-old male C57BL/6J (WT) mice[3] | Dosage: | 0.2, 0.5, 1 or 2.5 mg/kg | Administration: | Injected intraperitoneally every other day for 1 month | Result: | Attenuated progression of OA in ACLT mice. |
Animal Model: | Male nude mice (BALB/C nu/nu mice) (6-8-week)[1] | Dosage: | 0.25 mg/kg | Administration: | Intraperitoneally injected; every day; 16 days | Result: | The combined treatment with Cisplatin significantly suppressed the tumor volume. NRF2 protein levels in tumors were indeed decreased. |
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结构分类 | - Alkaloids
- Piperidine Alkaloids
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来源 | - Plants
- Saxifragaceae
- Dichroa febrifugaLour
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 20 mg/mL(48.23 mM;ultrasonic and adjust pH to 5 with HCl) 配制储备液 1 mM | 2.4115 mL | 12.0575 mL | 24.1150 mL | 5 mM | 0.4823 mL | 2.4115 mL | 4.8230 mL | 10 mM | 0.2411 mL | 1.2057 mL | 2.4115 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2 mg/mL (4.82 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (4.82 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2 mg/mL (4.82 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (4.82 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 0.67 mg/mL (1.62 mM); Clear solution
此方案可获得 ≥ 0.67 mg/mL (1.62 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 6.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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