| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
CXCR4
Burixafor HBr targets the CXCR4 receptor, a chemokine receptor that plays a crucial role in the migration of stem cells. It acts as a CXCR4 antagonist, binding to the chemokine receptor CXCR4 to stop stromal derived factor-1 (SDF-1 or CXCL12) from binding and subsequent receptor activation. By disrupting the CXCL12/CXCR4 axis, Burixafor facilitates the release of hematopoietic stem and progenitor cells from the bone marrow into the blood. |
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| ln Vitro |
TG-0054, a well water soluble anti-angiogenic drug that is of potential value in treating choroid neovascularization. After determining the influence of process parameters on particle size and drug loading, spherical microparticles syringeable through a 27 G needle, with a mean diameter of 7.6 μm, 10% w/w TG-0054 loading, sustained in vitro drug release for at least 6 months, and low residual organic solvent content (~ 1 ppb/mg) were prepared.
In vitro studies of Burixafor have focused on its sustained release formulation. Spherical microparticles with a mean diameter of 7.6 μm and 10% w/w TG-0054 loading were prepared, which showed sustained in vitro drug release for at least 6 months. The compound has been evaluated for its potential as an anti-angiogenic agent. The cellular activity is primarily assessed through its ability to antagonize CXCR4-mediated signaling in cell lines expressing the receptor. |
| ln Vivo |
Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits. Drug levels in the microparticle dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, 62.8 ± 22.6 μg/g vitreous, retina, and choroid-RPE, respectively, and similar to levels at one month. Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye, with the levels being 0.8 ± 0.5, 2.7 ± 2.8, and 4.9± 4.2 μg/g in vitreous, retina, and choroid-RPE, respectively, at one month, with no detectable drug at three months. Although surface degradation was evident, microparticles maintained their spherical structure during the 6 months in vitro study and the 3 months in vivo study, with the vitreal particle retention at 1 and 3 months being 60% and 27%, respectively.
In vivo studies have been conducted using intravitreal injection in New Zealand white rabbits. Microparticles and drug solution were assessed for drug delivery over 3 months. Drug levels in the microparticle-dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, and 62.8 ± 22.6 μg/g in vitreous, retina, and choroid-RPE, respectively. Intravitreal injection of plain drug solution resulted in significantly lower amounts in the dosed eye. Microparticles maintained their spherical structure during the 6-month in vitro and 3-month in vivo studies. |
| Enzyme Assay |
The binding affinity of Burixafor to CXCR4 is typically assessed using a radioligand binding assay. Membranes from cells expressing human CXCR4 are incubated with a radiolabeled CXCR4 ligand (e.g., [¹²⁵I]-SDF-1) and varying concentrations of Burixafor HBr. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 for displacement of the radioligand is calculated. Specific protocols and detailed conditions are not provided in the available summaries.
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| Cell Assay |
Weighed amount (5 to 10 mg) of TG-0054 loaded microparticles were dispersed in 1 ml of phosphate buffered saline (PBS, pH 7.4) containing 0.05% sodium azide. Sodium azide serves as a preservative to prevent the microbial degradation of the microparticle formulation. These dispersed microparticles were added to a dialysis bag (7Spectra/por®, MWCO 25 kDa) presealed at one end with a clip. After the addition of microparticle dispersion, the other side of the dialysis bag was closed. Dialysis bag containing the dispersion of microparticles was placed in drug release medium (10 ml PBS at pH 7.4 containing 0.05 % sodium azide) in a tube. The tubes were incubated at 37 °C while stirring the contents at 200 rpm. At discrete time intervals including 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr, 16 hr, 1 day, 2 days and every week thereafter, the entire release medium was replaced with fresh medium maintained at 37°C. The dissolution medium removed at each time interval was analyzed using a UV spectrophotometer and the amount of TG-0054 in the release medium was determined. All in vitro studies were carried out in triplicates.[1]
To evaluate the antagonistic activity of Burixafor on CXCR4, a cell-based assay using CXCR4-expressing cells (e.g., Jurkat T-cells) can be performed. Cells are loaded with a calcium-sensitive fluorescent dye and then pre-incubated with Burixafor HBr at various concentrations. The cells are stimulated with SDF-1 (CXCL12), and the intracellular calcium flux is measured using a fluorescence plate reader. The IC50 for inhibition of calcium flux is calculated. Alternatively, a chemotaxis assay can be used, where the compound's ability to inhibit SDF-1-induced cell migration is assessed using a Transwell chamber. |
| Animal Protocol |
The in vivo intravitreal delivery of TG-0054 from microparticle formulation was tested in male New Zealand white rabbits and compared with TG-0054 solution. Male New Zealand white rabbits weighing 2-3 kg were assigned to two groups. Group 1 (n = 6) received TG-0054-PLA microparticles intravitreally in one eye. Group 2 (n = 6) received TG-0054 solution intravitreally in both eyes. The rabbits were anaesthetized by intramuscular injection of ketamine : xyalazine mixture (50:10 v/v) in the hind limb of rabbits (400 μl/rabbit). Once the rabbits were in deep anesthesia, betadine solution was applied on eye surface and intravitreal injections were made using a 27G needle. Group 1 animals received 50 microliters of 300 mg microparticles/ml PBS (pH 7.4) [TG-0054-PLA microparticles with 10% drug loading; 15mg microparticles containing 1.5mg TG-0054/ 50μl] in the vitreal cavity of the right eye while the left eye was not dosed. Group 2 animals received 50 microliters of 20 mg TG-0054/ml PBS (pH 7.4) [1 mg/50 μl] in both eyes. After intravitreal injection, gentamicin ointment was applied at the injection site to prevent infections. The animals were regularly monitored for any abnormal signs. Three rabbits from each group were sacrificed at the end of 1 or 3 months post-dosing, in order to compare drug delivery between the formulations at the end of 1 and 3 months. Animals were euthanized by intravenous injection of sodium pentobarbital (150 mg/kg), and both eyes were enucleated and blood was collected. The eyes were immediately frozen in isopentane : dry ice bath and stored at −80 °C until further analysis.[1]
For in vivo pharmacokinetic and efficacy studies, the compound is typically administered via intravitreal injection in New Zealand white rabbits. The dosing regimen involves a single intravitreal injection of Burixafor-loaded microparticles or drug solution. Animals are euthanized at specified time points (e.g., 1 and 3 months), and ocular tissues (vitreous, retina, choroid-RPE) are collected for drug level analysis using LC-MS/MS. The retention of microparticles in the vitreous is assessed visually, and the percentage of particles retained is determined. |
| ADME/Pharmacokinetics |
Burixafor HBr is characterized as an orally bioavailable CXCR4 antagonist. Following intravitreal injection of microparticles in rabbits, drug levels in ocular tissues were sustained for at least 3 months. In contrast, the plain drug solution resulted in significantly lower amounts in the dosed eye, with no detectable drug at 3 months. This suggests that the microparticle formulation provides sustained release, extending the drug's residence time in the eye.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Burixafor HBr are not provided in the available sources. However, the compound is a research chemical intended for laboratory use only and is not approved for human therapeutic applications. The long-term retention of microparticles in the vitreous (60% at 1 month, 27% at 3 months) suggests a biocompatible profile. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Burixafor hydrobromide is the hydrobromide form of brissafor, a highly bioavailable, orally bioavailable CXC chemokine receptor 4 (CXCR4) inhibitor with hematopoietic stem cell (HSC) mobilization and chemosensitizing effects. After administration, brissafor binds to the chemokine receptor CXCR4, thereby preventing stromal cell-derived factor-1 (SDF-1 or CXCL12) from binding to the CXCR4 receptor, thus inhibiting receptor activation. This may induce the mobilization of hematopoietic stem cells and progenitor cells from the bone marrow to the peripheral circulation. Furthermore, brissafor-mediated mobilization of disseminated tumor cells (DTCs) from the bone marrow into the bloodstream may make these metastatic tumor cells more sensitive to chemotherapeutic drugs. CXCR4 is a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, playing a crucial role in chemotaxis and angiogenesis, and is upregulated in various tumor cell types. The CXCL12/CXCR4 interaction can induce hematopoietic cell retention in the bone marrow.
Burixafor HBr is also known as TG-0054. The compound is a well water-soluble anti-angiogenic drug of potential value in treating choroid neovascularization. Its primary application is in the mobilization of hematopoietic stem cells for transplantation. The compound is supplied with a purity of ≥98% for research purposes. It acts as a chemokine receptor antagonist specifically targeting the CXCR4 receptor. |
| Molecular Formula |
C27H52BRN8O3P
|
|---|---|
| Molecular Weight |
647.631345748901
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| Exact Mass |
646.31
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| Elemental Analysis |
C, 37.56; H, 7.00; Br, 27.76; N, 12.98; O, 11.12; P, 3.59
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| CAS # |
1191450-19-7
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| Related CAS # |
1191450-19-7 (HBr); 1191448-17-5 (free acid)
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| PubChem CID |
154575080
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| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
40
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| Complexity |
724
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC(CC1)NCCCNCC2CCC(CC2)CNC3=NC(=CC(=N3)N4CCN(CC4)CCP(=O)(O)O)N.Br
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| InChi Key |
ZXUVXYNBMUFEMK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H51N8O3P.BrH/c28-25-19-26(35-15-13-34(14-16-35)17-18-39(36,37)38)33-27(32-25)31-21-23-9-7-22(8-10-23)20-29-11-4-12-30-24-5-2-1-3-6-24;/h19,22-24,29-30H,1-18,20-21H2,(H2,36,37,38)(H3,28,31,32,33);1H
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| Chemical Name |
2-[4-[6-amino-2-[[4-[[3-(cyclohexylamino)propylamino]methyl]cyclohexyl]methylamino]pyrimidin-4-yl]piperazin-1-yl]ethylphosphonic acid;hydrobromide
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| Synonyms |
TG-0054; Burixafor; TG0054; Burixafor HBr; TG 0054; Burixafor HBr hydrate; Burixafor trihydrobromide trihydrate
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| HS Tariff Code |
2934.99.03.00
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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 (e.g. under nitrogen), 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) |
H2O: ~50 mg/mL (~65.0 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 20 mg/mL (26.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5441 mL | 7.7205 mL | 15.4409 mL | |
| 5 mM | 0.3088 mL | 1.5441 mL | 3.0882 mL | |
| 10 mM | 0.1544 mL | 0.7720 mL | 1.5441 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02478125
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