| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Ki: 18.3±0.5 nM (prolyl-tRNA synthetase)[2]
Halofuginone hydrochloride is a competitive inhibitor of prolyl-tRNA synthetase (PRS). By inhibiting this enzyme, halofuginone prevents the attachment of proline to its cognate tRNA, leading to the activation of the amino acid starvation response (AAR) via the GCN2 kinase pathway. This results in the inhibition of type-I collagen synthesis and the downregulation of matrix metalloproteinase 2 (MMP-2) gene expression. It also suppresses TGF-beta signaling, which contributes to its antifibrotic effects. Halofuginone hydrochloride is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-beta activity. |
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| ln Vitro |
Halofuginone hydrobromid competitively inhibits prolyl-tRNA synthetase by occupying the proline and tRNA binding pockets of prolyl-tRNA synthetase[1]. The IC 50 values of Halofuginone hydrobromid (1, 10, 100, 1000, 10000 nM; 48 h) in KYSE70 and A549 cells were 1.6 and 58.9 nM, respectively[1]. In KYSE70 and A549 cells, the IC 50 values of Halofuginone hydrobromid (1, 10, 100, 1000 nM; 24 h) against NRF2 protein were 22.3 and 37.2 nM, respectively. In KYSE70 and A549 cells, the IC50 values of Halofuginone hydrobromid against global protein synthesis were 22.6 and 45.7 nM, respectively[1]. Halofuginone hydrobromid increases voltage-gated K+ (Kv) current in pulmonary artery smooth muscle cells (PASMCs) and K+ current through KCNA5 channels in HEK cells transfected with KCNA5 gene. Halofuginone hydrobromid (0.03-1μM) inhibits receptor-operated Ca2+ entry (ROCE) in HEK cells transfected with calcium-sensing receptor gene and attenuates store-operated (SOCE) Ca2+ entry in PASMCs[5].
Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-beta activity. It is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated, and store-operated Ca2+ channels. The compound has antimalarial, anticoccidial, anti-inflammatory, and anticancer activities. The compound has antiparasitic effects in malaria, cryptosporidiosis, coccidiosis, toxoplasmosis, and leishmaniasis. It blocks fibrosis and tumor progression in a variety of different models. Halofuginone hydrochloride is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-beta activity. It has demonstrated significant anti-malaria, anti-inflammatory, anti-cancer, and anti-fibrotic properties. No specific IC50 values are reported. |
| ln Vivo |
Halofuginone hydrobromid (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates OA progression in mice with anterior cruciate ligament transection (ACLT). Lower concentrations (0.2 or 0.5 mg/kg) had minimal effects on subchondral bone, while higher concentrations (2.5 mg/kg) resulted in proteoglycan loss in articular cartilage[3]. Halofuginone hydrobromid (0.25 mg/kg; intraperitoneally injected; every day; 16 days) reduced NRF2 protein levels in tumors. Although there was no significant change in tumor volume between treatments with vehicle, halofuginone hydrobromid (0.25 mg/kg, intraperitoneally injected, every day) or cisplatin alone, the combination of halofuginone hydrobromid and cisplatin significantly inhibited tumor volume compared with treatment with halofuginone hydrobromid or cisplatin alone[1]. Intraperitoneal injection of Halofuginone (0.3 mg/kg, for 2 weeks) can partially reverse established pulmonary hypertension in mice[5].
Halofuginone hydrochloride is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-beta activity. It has demonstrated significant anti-malaria, anti-inflammatory, anti-cancer, and anti-fibrotic properties. The compound is under investigation in clinical trials for Duchenne muscular dystrophy (DMD). Halofuginone hydrochloride is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-beta activity. It has demonstrated significant anti-malaria, anti-inflammatory, anti-cancer, and anti-fibrotic properties. No specific in vivo activity data beyond clinical trial status are reported in the search results. |
| Enzyme Assay |
The binding of halofuginone to prolyl-tRNA synthetase (PRS) is measured by standard enzyme activity assays. Purified recombinant PRS is incubated with the compound, ATP, proline, and tRNA. The formation of prolyl-tRNA is measured by acid precipitation and scintillation counting, or by a fluorescence-based assay. The Ki of 18.3 nM is calculated.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutation. Concentration: 1, 10, 100, 1000, 10000 nM Incubation Duration: 24 h Experimental Results: The IC50s for NRF2 protein were 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. Cell Viability Assay[1] Cell Types: KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutation Concentration: 1, 10, 100, 1000, 10000 nM Incubation Duration: 48 h Experimental Results: The IC50s were 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. For cellular assays, fibroblasts (e.g., NIH/3T3) or hepatic stellate cells are seeded in 6- or 96-well plates. Cells are treated with halofuginone hydrochloride at concentrations of 1-1000 nM for 24-48 hours. Type-I collagen production is measured by ELISA (Procollagen type I C-peptide, PICP) or by Western blot for collagen type I. TGF-beta signaling is assessed by Western blot for p-Smad2/3 and total Smad2/3. For antiparasitic assays, Plasmodium falciparum-infected red blood cells are treated with halofuginone, and parasite growth is measured by [3H]-hypoxanthine incorporation. |
| Animal Protocol |
Animal/Disease Models:3-month-old male C57BL/6J (WT) mice[3]
Doses: 0.2, 0.5, 1 or 2.5 mg/kg Route of Administration: Injected intraperitoneally every other day for 1 month Experimental Results: Attenuated progression of OA in ACLT mice. For in vivo evaluation of Duchenne muscular dystrophy (DMD), the mdx mouse model (which lacks dystrophin) is used. Halofuginone hydrochloride (HT-100) is administered orally at doses of 10-100 microg/kg daily for 4-8 weeks. Muscle fibrosis is assessed by collagen quantification (hydroxyproline assay) and histology (Sirius Red staining). Muscle function is assessed by grip strength and running performance (treadmill). Serum creatine kinase (CK) levels are measured as a marker of muscle damage. Halofuginone hydrochloride is in a Phase 1b/2a clinical trial for DMD under the name HT-100. |
| ADME/Pharmacokinetics |
Halofuginone hydrochloride (C1₆H1₈BrCl2N3O3, MW = 451.14, purity ≥98%, CAS 1217623-74-9) is a solid powder (white to off-white). For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10-50 mM) can be prepared and stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo oral administration, it can be formulated in 0.5% methylcellulose/0.1% Tween-80 or in water. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for halofuginone hydrochloride are reported in the search results. Halofuginone has been studied in clinical trials for DMD and has been generally well-tolerated at the doses evaluated. Common adverse events in clinical trials include nausea, vomiting, and diarrhea. At high doses, halofuginone can cause weight loss and gastrointestinal toxicity. As a research-grade compound, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. No LD50 or formal toxicology studies are available.
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| References |
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| Additional Infomation |
Halofuginone hydrochloride is a research-grade compound derived from the natural product febrifugine, which has been used in traditional Chinese medicine as an antimalarial. Halofuginone is a specific inhibitor of prolyl-tRNA synthetase (PRS). PRS is an enzyme that attaches the amino acid proline to its cognate tRNA. By inhibiting PRS, halofuginone triggers a cellular stress response (the amino acid starvation response, AAR), which results in the downregulation of type-I collagen synthesis and the expression of matrix metalloproteinases (MMPs). This mechanism underlies its antifibrotic and anti-inflammatory activities. Halofuginone has been studied for the treatment of Duchenne muscular dystrophy (DMD), a severe genetic disorder characterized by muscle degeneration and fibrosis. It is also being studied for cancer, osteoarthritis, and parasitic diseases. The compound is for research use only and has not received full regulatory approval.
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| Molecular Formula |
C16H18BRCL2N3O3
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|---|---|
| Molecular Weight |
451.14
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| Exact Mass |
448.99
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| CAS # |
1217623-74-9
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| PubChem CID |
60196305
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| Appearance |
Typically exists as solid at room temperature
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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 |
C1C[C@H]([C@@H](NC1)CC(=O)CN2C=NC3=CC(=C(C=C3C2=O)Cl)Br)O.Cl
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| InChi Key |
XFFYBQUXAJOKAL-LDXVYITESA-N
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| InChi Code |
InChI=1S/C16H17BrClN3O3.ClH/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;hydrochloride
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| Synonyms |
RU-19110 hydrochloride
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2166 mL | 11.0830 mL | 22.1661 mL | |
| 5 mM | 0.4433 mL | 2.2166 mL | 4.4332 mL | |
| 10 mM | 0.2217 mL | 1.1083 mL | 2.2166 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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