Halofuginone (RU-19110)是febrifugine的衍生物，可抑制prolyl tRNA synthetase活性，Ki值为18.3nM。
Cas No.:55837-20-2
Sample solution is provided at 25 µL, 10mM.
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Halofuginone (RU-19110) is a derivative of febrifugine and can inhibit prolyl tRNA synthetase activity, with a Ki value of 18.3nM [1]. Halofuginone can induce pulmonary vasodilation by activating Kv channels and blocking voltage-dependent Ca2+ channels (VDCCs) and receptor-operated and store-operated Ca2+ channels[2]. Halofuginone has been widely used to inhibit collagen synthesis and alleviate liver and lung fibrosis in animals[3].
In vitro, Halofuginone treatment for 24 hours significantly inhibited the proliferation of U937 cells, OCI-AML3 cells and MV4-11 cells, with IC50 values of 0.06μM, 0.05μM and 0.09μM, respectively[4]. The 5nM Halofuginone treatment for 48 hours significantly inhibited the IL-2-mediated cell proliferation in activated mouse T cells and promoted cell apoptosis[5]. Treatment with 100nM Halofuginone for 24 hours significantly reduced the mRNA and protein levels of NRF2 in A549 cells and decreased the expression of NRF2 target genes[6].
In vivo, Halofuginone treatment via intraperitoneal injection at a dose of 1mg/kg every other day for one month significantly alleviated the progression of osteoarthritis in the anterior cruciate ligament transection (ACLT) mouse model, reducing the activity of TGF-β in subchondral bone and abnormal angiogenesis[7]. A weekly five-time intraperitoneal injection of 0.25mg/kg dose of Halofuginone, for a duration of 4 weeks, significantly reduced the tumor volume in mice carrying human-derived uterine lymphoma (UL) xenograft tumors, without altering the mice's body weight[8].
References:
[1] Keller T L, Zocco D, Sundrud M S, et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase[J]. Nature chemical biology, 2012, 8(3): 311-317.
[2] Jain P P, Zhao T, Xiong M, et al. Halofuginone, a promising drug for treatment of pulmonary hypertension[J]. British journal of pharmacology, 2021, 178(17): 3373-3394.
[3] Pines M, Nagler A. Halofuginone: a novel antifibrotic therapy[J]. General Pharmacology: The Vascular System, 1998, 30(4): 445-450.
[4] Shi L, Zhao M, Meng C, et al. Halofuginone exerts broad-spectrum cytotoxic effects by regulating p-eIF2α-S100A8/A9-calcium signaling, inhibiting global protein synthesis, and reversing the resistance of idarubicin in acute myeloid leukemia[J]. Chinese Medicine, 2026, 21(1): 7.
[5] Chu T L H, Guan Q, Nguan C Y C, et al. Halofuginone suppresses T cell proliferation by blocking proline uptake and inducing cell apoptosis[J]. International Immunopharmacology, 2013, 16(4): 414-423.
[6] Tsuchida K, Tsujita T, Hayashi M, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation[J]. Free Radical Biology and Medicine, 2017, 103: 236-247.
[7] Cui Z, Crane J, Xie H, et al. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone[J]. Annals of the rheumatic diseases, 2016, 75(9): 1714-1721.
[8] Koohestani F, Qiang W, MacNeill A L, et al. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model[J]. Human Reproduction, 2016, 31(7): 1540-1551.
Halofuginone (RU-19110)是febrifugine的衍生物，可抑制prolyl tRNA synthetase活性，Ki值为18.3nM[1]。Halofuginone可通过激活Kv通道并阻断电压依赖性Ca2+通道(VDCCs)以及受体介导型和储存介导型Ca2+通道，诱导肺血管舒张[2]。Halofuginone已被广泛用于抑制胶原合成，并减轻动物的肝脏和肺纤维化[3]。
在体外，Halofuginone处理24小时显著抑制了U937细胞、OCI-AML3细胞和MV4-11细胞的增殖，IC50值分别为0.06μM、0.05μM和0.09μM[4]。5nM的Halofuginone处理48小时显著抑制了活化小鼠T细胞中IL-2介导的细胞增殖，并促进了细胞凋亡[5]。使用100nM的Halofuginone处理A549细胞24小时，显著降低了NRF2的mRNA和蛋白水平，同时也降低了NRF2靶基因的表达[6]。
在体内，每隔一天腹腔注射1mg/kg剂量的Halofuginone，持续一个月，显著减轻了前交叉韧带横断(ACLT)小鼠模型中骨关节炎的进展，降低了软骨下骨中TGF-β的活性和异常血管生成[7]。每周五次腹腔注射0.25mg/kg剂量的Halofuginone，持续4周，显著减小了携带人源性子宫淋巴瘤(UL)异种移植瘤小鼠的肿瘤体积，且未改变小鼠的体重[8]。
| Cell experiment [1]: | |
Cell lines | U937 cells |
Preparation Method | U937 cells were cultured at 37°C and 5% CO2 in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS). U937 cells were plated at a density of 1×105 cells/ml in a 96-well plate with growth medium for 24h, and were incubated with the different concentrations of Halofuginone (0, 0.001, 0.01, 0.1, and 1µM) for 24h, then analyzed the cell viability. |
Reaction Conditions | 0, 0.001, 0.01, 0.1, and 1µM; 24h |
Applications | Halofuginone treatment significantly inhibited cell viability of U937 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | NOD-scid IL2Rγnull mice |
Preparation Method | Primary UL cells were grafted under the renal capsule of adult, ovariectomized female NOD-scid IL2Rγnull mice (NSG) that were supplemented with subcutaneous implantation of slow-releasing estradiol (E2) + progesterone (P4) hormone pellets (0.8mg E2, 75.2mg P4 and 4mg cholesterol). Four weeks after xenograft implantations were carried out, two mice were harvested for an initial check of the tumor growth for each implantation scheme and the tumor tissues collected at this time were designated as the time zero control point for tumor size. The remaining xenografted mice were then randomly divided into the groups for Halofuginone or vehicle (0.5% v/v DMSO in saline) treatment via intraperitoneal injection at 100µl/10g. Halofuginone group: 0.25mg/kg Halofuginone (i.p.) five times per week. After 4 weeks of treatment, mice were harvested for measurement of tumor volume. |
Dosage form | 0.25mg/kg; five times per week for 4 weeks; i.p. |
Applications | Halofuginone treatment reduced the tumor volume in mice carrying UL xenograft tumors. |
References: | |
| Cas No. | 55837-20-2 | SDF | |
| 别名 | 常山酮; RU-19110 | ||
| Canonical SMILES | O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3 | ||
| 分子式 | C16H17BrClN3O3 | 分子量 | 414.68 |
| 溶解度 | DMSO : 9 mg/mL (21.70 mM) | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4115 mL | 12.0575 mL | 24.115 mL |
| 5 mM | 482.3 μL | 2.4115 mL | 4.823 mL |
| 10 mM | 241.1 μL | 1.2057 mL | 2.4115 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，
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2.
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