Halofuginone  (Synonyms: RU-19110)

Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a K_i of 18.3 nM^[1][2]. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity^[3][4]. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca²⁺ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects^[5].

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 IC₅₀ of 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 attenuates store-operated Ca²⁺ entry (SOCE) in PASMC^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

414.68

C₁₆H₁₇BrClN₃O₃

55837-20-2

Solid

White to off-white

O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3

Room temperature in continental US; may vary elsewhere.

• [1]. Tsuchida K, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radic Biol Med. 2017 Feb;103:236-247.  [Content Brief]

  [2]. Keller TL, et al. Halofuginone and other Febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12;8(3):311-7.  [Content Brief]

  [3]. Cui Z, et al. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Ann Rheum Dis. 2016 Sep;75(9):1714-21.  [Content Brief]

  [4]. Tracy L McGaha, et al. Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming-growth-factor-beta-mediated Smad3 activation in fibroblasts. J Invest Dermatol. 2002 Mar;118(3):461-70.  [Content Brief]

  [5]. Pritesh P Jain, et al. Halofuginone, a Promising Drug for Treatment of Pulmonary Hypertension. Br J Pharmacol. 2021 Mar 10.  [Content Brief]