| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
Halofuginone hydrobromide (RU-19110) is a Febrifugine derivative that acting as a competitive prolyl-tRNA synthetase inhibitor (Ki = 18.3 nM) with anti-inflammatory, anti-malaria, anti-cancer, anti-fibrosis activity.
| 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].
|
|---|---|
| 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].
|
| 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. |
| 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. |
| 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 |
Halofuginone Hydrobromide is the hydrobromide salt of halofuginone, a semisynthetic quinazolinone alkaloid anticoccidial derived from the plant Dichroa febrifuga, with antifibrotic and potential antineoplastic activities. Halofuginone specifically inhibits collagen type I gene expression and matrix metalloproteinase 2 (MMP-2) gene expression, which may result in the suppression of angiogenesis, tumor stromal cell development, and tumor cell growth. These effects appear to be due to halofuginone-mediated inhibition of the collagen type I and MMP-2 promoters. Collagen type I and MMP-2 play important roles in fibro-proliferative diseases.
See also: Halofuginone Hydrobromide (annotation moved to). |
| Molecular Formula |
C₁₆H₁₈BR₂CLN₃O₃
|
|---|---|
| Molecular Weight |
495.59
|
| Exact Mass |
492.94
|
| CAS # |
64924-67-0
|
| Related CAS # |
Halofuginone;55837-20-2
|
| PubChem CID |
400771
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
595.8ºC at 760 mmHg
|
| Melting Point |
247° (dec)
|
| Flash Point |
314.1ºC
|
| LogP |
3.171
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
25
|
| Complexity |
533
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3.Br
|
| InChi Key |
SJUWEPZBTXEUMU-LDXVYITESA-N
|
| 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
|
| Chemical Name |
7-bromo-6-chloro-3-[3-[(2S,3R)-3-hydroxypiperidin-2-yl]-2-oxopropyl]quinazolin-4-one;hydrobromide
|
| Synonyms |
RU19110 RU-19110 hydrobromide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~100.89 mM)
H2O : ~2.6 mg/mL (~5.25 mM) |
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
