Halofuginone hydrochloride (RU-19110), a derivative of Febrifugine, functions as a competitive inhibitor of prolyl-tRNA synthetase, displaying a Ki value of 18.3 nM. This compound effectively inhibits type-I collagen synthesis, providing therapeutic benefits in osteoarthritis (OA) by impeding TGF-β signaling. Additionally, it serves as a potent pulmonary vasodilator, mainly through the activation of Kv channels and the inhibition of various calcium channels including voltage-gated, receptor-operated, and store-operated ones. Beyond its vascular effects, Halofuginone hydrochloride exhibits a broad spectrum of biological activities, including anti-malarial, anti-inflammatory, anti-cancer, and anti-fibrotic properties, supported by multiple studies.

Halofuginone hydrochloride通过与脯氨酰-tRNA合成酶的活性位点相结合，竞争性抑制了该酶的活性，进而影响脯氨酸及tRNA的结合[1]。在KYSE70和A549细胞系中，经48小时处理后，Halofuginone hydrochloride的半抑制浓度(IC50)分别为1.6nM和58.9nM[1]。此外，对于NRF2蛋白，24小时内在同样的细胞系中，该化合物的IC50值分别为22.3nM和37.2nM。关于细胞整体蛋白质合成的影响，该化合物的IC50值在KYSE70和A549细胞中分别为22.6nM和45.7nM[1]。Halofuginone hydrobromid还能增强肺动脉平滑肌细胞(PASMC)中的电压门控K+ (Kv)电流，以及转染KCNA5基因后，通过KCNA5通道在HEK细胞中的K+电流。对于转染钙敏感受体基因的HEK细胞，该化合物在0.03-1μM浓度范围内，能抑制受体操纵的Ca2+内流(ROCE)及减少PASMC中钙池操纵的(SOCE)Ca2+内流[5]。

Halofuginone hydrochloride (0.2, 0.5, 1或2.5 mg/kg；每隔一天腹腔内注射，连续1个月) 显著减缓了前交叉韧带横断(ACLT)小鼠的骨关节炎(OA)进展。低剂量(0.2或0.5 mg/kg)对软骨下骨影响较小，而高剂量(2.5 mg/kg)则会导致关节软骨中蛋白聚糖的损失[3]。此外，每日腹腔内注射Halofuginone hydrochloride (0.25 mg/kg，连续16天)能降低肿瘤中NRF2蛋白水平。尽管使用载体、Halofuginone hydrochloride (0.25 mg/kg，每日腹腔内注射)或单独顺铂治疗肿瘤体积无显著差异，但Halofuginone hydrochloride与顺铂联合治疗比单独应用任一化合物更能显著抑制肿瘤体积[1]。此外，连续2周腹腔内注射Halofuginone (0.3mg/kg)可部分逆转小鼠已形成的肺动脉高压[5]。