| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Halofuginone lactate targets prolyl-tRNA synthetase (PRS) as a competitive inhibitor with a Ki of 18.3 nM. It inhibits the attachment of proline to its cognate tRNA, thereby blocking protein synthesis. This leads to activation of the amino acid response (AAR) pathway and inhibition of TGF-beta signaling. It also inhibits type-I collagen synthesis, activates Kv channels, and blocks voltage-gated and store-operated Ca2+ channels, contributing to its vasodilatory and anti-fibrotic effects.
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| ln Vitro |
Halofuginone lactate is a potent inhibitor of prolyl-tRNA synthetase with a Ki of 18.3 nM. It inhibits type-I collagen synthesis and suppresses TGF-beta activity, leading to anti-fibrotic effects. It also acts as a pulmonary vasodilator by activating Kv channels and blocking Ca2+ channels. In vitro, it has anti-inflammatory and anti-cancer activity. The compound is commonly used in research at concentrations ranging from 1 nM to 10 uM depending on the cell type and assay.
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| ln Vivo |
Halofuginone lactate has shown in vivo efficacy in a mouse model of multiple sclerosis by inhibiting T(H)17-driven autoimmunity through activation of the amino acid response (AAR) pathway. It attenuates osteoarthritis (OA) by inhibition of TGF-beta activity and H-type vessel formation in subchondral bone. It also reduces fibrosis and has shown anti-inflammatory and anti-cancer effects. The compound is orally active and has a Ki of 18.3 nM.
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| Enzyme Assay |
Prolyl-tRNA synthetase inhibition can be measured using an aminoacylation assay. Procedure: Recombinant human prolyl-tRNA synthetase (10 nM) is incubated with varying concentrations of Halofuginone lactate (0.1-1000 nM) in assay buffer (50 mM HEPES, pH 7.5, 20 mM KCl, 10 mM MgCl2, 2 mM DTT, 0.1 mg/mL BSA). The reaction is initiated by adding [3H]-proline (1 microM) and tRNAPro (10 microM). After 10 minutes at 37degC, the reaction is spotted onto filter paper, washed with cold TCA, and counted. The Ki of 18.3 nM is calculated from the dose-response curve using Lineweaver-Burk analysis.
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| Cell Assay |
Cellular activity can be assessed in TGF-beta-responsive fibroblasts. Procedure: Human dermal fibroblasts are seeded in 6-well plates (2x10⁵ cells/well) and cultured for 24 hours. Cells are treated with varying concentrations of Halofuginone lactate (1-1000 nM) for 2 hours, then stimulated with TGF-beta (5 ng/mL) for 24 hours. Type-I collagen levels in the culture supernatant are measured by ELISA. SMAD3 phosphorylation is analyzed by Western blotting. Cell viability is assessed by MTT assay. A reduction in collagen secretion and p-SMAD3 indicates efficacy.
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| Animal Protocol |
In vivo efficacy can be evaluated in a mouse model of osteoarthritis. Procedure: Male C57BL/6 mice (10 weeks) undergo destabilization of the medial meniscus (DMM) surgery to induce OA. Mice are randomized into groups (n=10). Halofuginone lactate is dissolved in PBS and administered intraperitoneally at doses of 0.1, 0.3, and 1 mg/kg three times per week for 8 weeks. The positive control group receives a TGF-beta inhibitor. Osteoarthritis severity is assessed by micro-CT and histological scoring (OARSI score) of the knee joints. Subchondral bone H-type vessel formation is analyzed by CD31/Emcn immunofluorescence. A reduction in OA score indicates efficacy.
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| ADME/Pharmacokinetics |
Halofuginone lactate is orally active. Specific PK parameters are not provided, but it is known to be absorbed when administered via oral or intraperitoneal routes. The compound has a Ki of 18.3 nM for its target, suggesting that low doses may be effective. It is soluble in DMSO (35 mg/mL) and is stored as a powder at -20degC.
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| Toxicity/Toxicokinetics |
Toxicology data for Halofuginone lactate is not provided. As a prolyl-tRNA synthetase inhibitor, potential on-target toxicities may include effects on collagen synthesis and fibrosis. However, the compound has been studied in preclinical models with acceptable tolerability. It is for research use only and is not an approved drug. Standard safety precautions for handling research chemicals should be followed.
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| References |
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| Additional Infomation |
Halofuginone lactate is a derivative of febrifugine, a natural quinazolinone-containing compound found in the Chinese herb Dichroa febrifuga. It is a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM. The compound specifically inhibits type-I collagen synthesis, activates Kv channels, and blocks Ca2+ channels. It attenuates osteoarthritis by inhibiting TGF-beta activity and has anti-malaria, anti-inflammatory, anti-cancer, and anti-fibrosis effects. It is for research use only.
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| Molecular Formula |
C19H23BRCLN3O6
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|---|---|
| Molecular Weight |
504.76
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| Exact Mass |
503.046
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| CAS # |
82186-71-8
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| PubChem CID |
46905589
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| Appearance |
White to off-white solid powder
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| Boiling Point |
595.8ºC at 760mmHg
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| Flash Point |
314.1ºC
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| LogP |
1.665
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
592
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(O)(C)C(=O)O.O=C1N(CC(=O)C[C@@H]2NCCC[C@H]2O)C=NC2C=C(C(=CC1=2)Cl)Br
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| InChi Key |
GATQERNJKZPJNX-LIOBNPLQSA-N
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| InChi Code |
InChI=1S/C16H17BrClN3O3.C3H6O3/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;1-2(4)3(5)6/h5-6,8,14-15,19,23H,1-4,7H2;2,4H,1H3,(H,5,6)/t14-,15+;/m1./s1
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| Chemical Name |
7-bromo-6-chloro-3-[3-[(2R,3S)-3-hydroxypiperidin-2-yl]-2-oxopropyl]quinazolin-4-one;2-hydroxypropanoic acid
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| Synonyms |
RU-19110 lactate
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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 | 1.9811 mL | 9.9057 mL | 19.8114 mL | |
| 5 mM | 0.3962 mL | 1.9811 mL | 3.9623 mL | |
| 10 mM | 0.1981 mL | 0.9906 mL | 1.9811 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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