BX 471 (Synonyms: ZK-811752) |
| Catalog No.GC14519 |
CCR1 antagonist,potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 217645-70-0
Sample solution is provided at 25 µL, 10mM.
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Ki: 1 nM to 5.5 nM
The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. BX 471 is a potent, selective, and orally active antagonist of the CC Chemokine Receptor-1.
In vitro: Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1a, RANTES, and monocyte chemotactic protein-3 with high affinity. BX 471 was a potent functional antagonist based on its ability to inhibit plenty of CCR1-mediated effects. BX 471 also demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors [1].
In vivo: Pharmacokinetic studies demonstrated that BX 471 was orally active with a 60% bioavailability in dogs. Furthermore, in a rat experimental allergic encephalomyelitis model of multiple sclerosis, BX 471 effectively reduces disease [1].
Clinical trial: Up to now, BX 471 is still in the preclinical development stage.
Reference:
[1] Liang M, Mallari C, Rosser M, Ng HP, May K, Monahan S, Bauman JG, Islam I, Ghannam A, Buckman B, Shaw K, Wei GP, Xu W, Zhao Z, Ho E, Shen J, Oanh H, Subramanyam B, Vergona R, Taub D, Dunning L, Harvey S, Snider RM, Hesselgesser J, Morrissey MM, Perez HD. Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem. 2000 Jun 23;275(25):19000-8.
Animal experiment: | Fasted male beagle dogs (n=3 per treatment group) are given BX471 either by oral gavage or by intravenous injection via the cephalic vein at a dose of 4 mg/kg. The compound is dissolved in a vehicle of 40% aqueous cyclodextrin. Serial blood samples are collected utilizing an in-dwelling catheter in the jugular vein at the indicated time points up to 6 h post-dosing. EDTA is used as an anticoagulant. The samples are centrifuged (1000× g for 10 min at 4°C), and plasma is stored frozen until analyzed for drug levels by HPLC-MS (electrospray mode operated under a positive ion mode). Plasma samples are thawed and denatured by the addition of four parts of ice-cold methanol containing a fixed amount of an internal standard to one part of plasma. The resulting protein precipitate is removed by centrifugation at 5000× g, and the supernatants are analyzed directly. Concurrently plasma calibration standards of BX471 are prepared over the range of quantification, processed, and analyzed under identical conditions. A FISONS, VG Platform single quadrupole instrument is used in these analyses with an electrospray inlet operated at 3.57 kV. Chromatographic separation is accomplished using a YMC AQ octadecyl silane reversed phase column (4.6×250 mm) following a short isocratic elution method (35% methanol, 65% water containing 0.1% trifluoroacetic acid). The total column flow (1 mL/min) is split post-column to infuse 50 μL/min into the mass spectrometer. The chromatograms are collected over a total run time of 7.5 min/sample following a 50-μL injection on the column. The ions are collected in a single ion positive ionization mode. A calibration curve for quantification is generated by plotting ion current ratios between the internal standard peak and the analyte in the plasma standards over the quantification range. Calculations of percent oral availability is deduced from the area under curve measurements. Pharmacokinetic parameters are calculated using WinNonLin version 3.0. |
References: [1]. Liang M, et al. Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem. 2000 Jun 23;275(25):19000-8. | |
| Cas No. | 217645-70-0 | SDF | |
| Synonyms | ZK-811752 | ||
| Chemical Name | (R)-1-(5-chloro-2-(2-(4-(4-fluorobenzyl)-2-methylpiperazin-1-yl)-2-oxoethoxy)phenyl)urea | ||
| Canonical SMILES | ClC1=CC=C(C(NC(N)=O)=C1)OCC(N2[C@H](C)CN(CC(C=C3)=CC=C3F)CC2)=O | ||
| Formula | C21H24ClFN4O3 | M.Wt | 434.89 |
| Solubility | DMF: 30 mg/mL,DMF:PBS (pH 7.2) (1:9): 0.1 mg/mL,DMSO: 25 mg/mL,Ethanol: 14 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2994 mL | 11.4972 mL | 22.9943 mL |
| 5 mM | 0.4599 mL | 2.2994 mL | 4.5989 mL |
| 10 mM | 0.2299 mL | 1.1497 mL | 2.2994 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)
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