| Size | Price | Stock | Qty |
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| 5mg |
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| 50mg |
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| 250mg |
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| Targets |
Halofuginone hydrobromide targets prolyl-tRNA synthetase, an enzyme essential for protein synthesis, with a Ki of 18.3 nM. It specifically inhibits type I collagen synthesis and blocks transforming growth factor-beta-mediated Smad3 activation in fibroblasts. The compound also inhibits matrix metalloproteinase 2 (MMP-2) gene expression, thereby inhibiting angiogenesis, tumor stromal cell development, and tumor cell growth. Its antifibrotic effects are mediated through inhibition of collagen synthesis and modulation of the TGF-β signaling pathway.
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| ln Vitro |
By occupying the proline and tRNA binding sites of prolyl-tRNA synthetase, halofuginone competitively inhibits prolyl-tRNA synthetase [1]. In KYSE70 and A549 cells, halofuginone (1, 10, 100, 1000, and 10,000 nM; 48 hours) had an IC50 of 114.6 and 58.9 nM, respectively. In KYSE70 and A549 cells, the IC50 of halofuginone (1, 10, 100, and 1000 nM; 24 hours) against NRF2 protein was 22.3 and 37.2 nM, respectively. In KYSE70 and A549 cells, halofuginone's IC50 values for total protein synthesis were 22.6 and 45.7 nM, respectively [1]. Halofuginone raises K+ currents via KCNA5 channels in HEK cells transfected with the KCNA5 gene and voltage-gated K+ (Kv) currents in pulmonary artery smooth muscle cells (PASMC). In HEK cells transfected with calcium-sensing receptor genes, halofuginone (0.03-1μM) decreases receptor-operated Ca2+ influx (ROCE), and in PASMC, it attenuates store-operated Ca2+ influx (SOCE) [5].
In vitro studies have demonstrated that Halofuginone hydrobromide is a potent inhibitor of type I collagen synthesis and Smad3 activation. It inhibits angiogenesis, tumor stromal cell development, and tumor cell growth. The compound is a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM. Its ability to inhibit collagen synthesis and modulate TGF-β signaling makes it a valuable tool for studying fibrosis, cancer, and autoimmune diseases. Halofuginone has been shown to inhibit the development of new blood vessels and prevent intimal hyperplasia at vascular anastomoses. |
| ln Vivo |
In mice with anterior cruciate ligament transection (ACLT), halofuginone (0.2, 0.5, 1, or 2.5 mg/kg; i.p. every other day for one month) slows the progression of osteoarthritis. Higher quantities (2.5 mg/kg) result in the loss of proteoglycans in articular cartilage, while lower amounts (0.2 or 0.5 mg/kg) had little effect on subchondral bone [3]. In malignancies, halofuginone (0.25 mg/kg; i.p.; daily; 16 days) lowers the levels of NRF2 protein. Despite this, the tumor volume did not significantly alter between the vehicle, cisplatin alone, or halogenone (0.25 mg/kg, intraperitoneal injection, daily) treatments. When halopentone and cisplatin were administered together, the tumor volume was dramatically reduced as opposed to when either drug was used alone [1]. In rats with established pulmonary hypertension, halopentone injections intraperitoneally (0.3 mg/kg for two weeks) can partially correct the condition [5].
In vivo, Halofuginone hydrobromide has been studied for its potential therapeutic applications in fibrosis, autoimmune diseases, and cancer. It has been shown to inhibit type I collagen synthesis and skin sclerosis. The compound prevents intimal hyperplasia at vascular anastomoses by inhibiting angiogenesis. Halofuginone is also used in the treatment or prevention of coccidiosis in both humans and animals. Its antifibrotic, antiangiogenic, and anticancer activities make it a promising candidate for further development. |
| Enzyme Assay |
In vitro non-cell enzyme assays for Halofuginone hydrobromide involve measuring prolyl-tRNA synthetase inhibition using purified enzyme and a radiolabeled substrate (proline and tRNA). The compound is incubated with enzyme and substrate, and aminoacylation activity is measured by filter binding or scintillation counting. Ki values are calculated from steady-state kinetic analysis. Type I collagen synthesis inhibition can be assessed using cell-free translation systems or purified collagen assays.
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| Cell Assay |
Cell viability assay [1]
Cell Types: from human esophageal cancer KYSE70 cells carrying NRF2 gene mutations and A549 cells carrying KEAP1 gene mutations Tested Concentrations: 1, 10, 100, 1000, 10000 nM Incubation Duration: 48 hrs (hours) Experimental Results: IC50 KYSE70 and The concentrations in A549 cells were 114.6 and 58.9 nM, respectively. Western Blot Analysis[1] Cell Types: Human esophageal cancer KYSE70 cells with NRF2 gene mutation and A549 cells with KEAP1 gene mutation Tested Concentrations: 1, 10, 100, 1000 nM Incubation Duration: 24 hrs (hours) Experimental Results: IC50 of NRF2 KYSE70 and proteins in A549 cells were 22.3 and 37.2 nM, respectively. In vitro cell-based assays for Halofuginone hydrobromide use fibroblasts, cancer cells, or other relevant cell lines. Cells are treated with Halofuginone at various concentrations, and parameters assessed include type I collagen synthesis (by ELISA or Western blotting), Smad3 activation (by Western blotting using phospho-Smad3 antibodies), cell proliferation (MTT or CCK-8 assays), angiogenesis (tube formation assays using endothelial cells), and MMP-2 expression (by zymography or Western blotting). |
| Animal Protocol |
Animal/Disease Models: Male nude mice (BALB/C nu/nu (nude) mice) (6-8 weeks) [1]
Doses: 0.25 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; 16 days Experimental Results: Combined treatment with cisplatin demonstrated significant Dramatically inhibited tumor volume. NRF2 protein levels were indeed diminished in the tumors. In vivo animal studies for Halofuginone hydrobromide employ rodent models of fibrosis (e.g., bleomycin-induced pulmonary fibrosis, skin sclerosis), cancer (xenograft models), and autoimmune diseases. The compound is administered orally or intraperitoneally, and parameters assessed include collagen deposition (histology, hydroxyproline content), tumor growth (tumor volume measurements), angiogenesis (CD31 staining), Smad3 activation, and evaluation of systemic toxicity. |
| ADME/Pharmacokinetics |
Halofuginone hydrobromide has a molecular weight of 495.59 g/mol and a molecular formula of C₁₆H₁₈Br₂ClN₃O₃. It is also known as RU-19110 hydrobromide. The compound is soluble in DMSO and should be stored under appropriate conditions as recommended by the manufacturer. Detailed pharmacokinetic parameters have been characterized in preclinical studies but are not extensively documented in the public literature.
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| Toxicity/Toxicokinetics |
Halofuginone hydrobromide is generally well-tolerated at therapeutic doses, but adverse effects may include gastrointestinal disturbances, hepatotoxicity, and cardiotoxicity at high doses. The compound is classified as a research reagent and is not intended for human therapeutic use without appropriate regulatory approval. Comprehensive toxicological data are available from preclinical studies.
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| References |
[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.
[2]. Keller TL, et al. Halofuginone and other Febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12;8(3):311-7. [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. [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. [5]. Pritesh P Jain, et al. Halofuginone, a Promising Drug for Treatment of Pulmonary Hypertension. Br J Pharmacol. 2021 Mar 10. |
| Additional Infomation |
Halovigidone hydrobromide is the hydrobromide salt of halovigidone, a semi-synthetic quinazolinone alkaloid anticoccidial drug derived from the plant Dichroa febrifuga, possessing antifibrotic and potential antitumor activity. Halovigidone specifically inhibits the expression of type I collagen and matrix metalloproteinase 2 (MMP-2) genes, potentially leading to inhibition of angiogenesis, tumor stromal cell development, and tumor cell growth. These effects appear to be due to halovigidone-mediated inhibition of the type I collagen and MMP-2 promoters. Type I collagen and MMP-2 play important roles in fibroproliferative diseases.
See also: Halovigidone hydrobromide (note moved to). Halofuginone hydrobromide is a semisynthetic quinazolinone alkaloid derived from febrifugine. It is a specific inhibitor of type I collagen synthesis and a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM. The compound has anticoccidial, antifibrotic, and potential antineoplastic activities. It is studied for fibrosis, autoimmune diseases, and cancer. Not approved for clinical use; intended for research purposes only. |
| Molecular Formula |
C₁₆H₁₈BR₂CLN₃O₃
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| Molecular Weight |
495.59
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| Exact Mass |
492.94
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| CAS # |
64924-67-0
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| Related CAS # |
Halofuginone;55837-20-2
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| PubChem CID |
400771
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| Appearance |
White to off-white solid powder
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| Boiling Point |
595.8ºC at 760 mmHg
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| Melting Point |
247° (dec)
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| Flash Point |
314.1ºC
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| LogP |
3.171
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
533
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3.Br
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| InChi Key |
SJUWEPZBTXEUMU-LDXVYITESA-N
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| InChi Code |
InChI=1S/C16H17BrClN3O3.BrH/c17-11-6-13-10(5-12(11)18)16(24)21(8-20-13)7-9(22)4-14-15(23)2-1-3-19-14;/h5-6,8,14-15,19,23H,1-4,7H2;1H/t14-,15+;/m0./s1
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| Chemical Name |
7-bromo-6-chloro-3-[3-[(2S,3R)-3-hydroxypiperidin-2-yl]-2-oxopropyl]quinazolin-4-one;hydrobromide
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| Synonyms |
RU19110 RU-19110 hydrobromide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~100.89 mM)
H2O : ~2.6 mg/mL (~5.25 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0178 mL | 10.0890 mL | 20.1780 mL | |
| 5 mM | 0.4036 mL | 2.0178 mL | 4.0356 mL | |
| 10 mM | 0.2018 mL | 1.0089 mL | 2.0178 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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