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| 5mg |
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| 25mg |
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Purity: ≥98%
BX471 HCl (also known as BX-471; ZK-811752) is a novel, oral and non-peptide antagonist of CCR1 (CC chemokine receptor-1) with potential anti-inflammatory activity. It has a Ki of 1 nM for human CCR1, suggesting that it could be helpful in the management of inflammatory chronic illnesses. Compared to CCR2, CCR5, and CXCR4, BX471 shows a 250-fold preference for CCR1. When it comes to treating autoimmune disorders, CCR1 is a top therapeutic target. BX 471 exhibits a selectivity for CCR1 that is more than 10,000 times greater than that of 28 G-protein-coupled receptors. Competition binding studies demonstrated that BX 471 exhibited a high degree of affinity in disabling the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3); K(i) varied between 1 and 5.5 nm. BX 471 demonstrated strong functional antagonist properties by blocking several CCR1-mediated processes, such as leukocyte migration, extracellular acidification rate increase, Ca(2+) mobilization, and CD11b expression. Additionally, in a rat model of experimental allergic encephalomyelitis associated with multiple sclerosis, BX 471 effectively lowers disease.
| Targets |
MIP-1α-CCR1 ( Ki = 1 nM ); RANTES-CCR1 ( Ki = 2.8 nM ); MCP-3-CCR1 ( Ki = 5.5 nM )
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| Enzyme Assay |
BX471 (also known as ZK-811752) is a novel, oral and non-peptide CCR1 (CC chemokine receptor-1) antagonist that has a Ki of 1 nM for human CCR1. It may be helpful in the management of chronic inflammatory conditions. Compared to CCR2, CCR5, and CXCR4, BX471 shows a 250-fold preference for CCR1. When it comes to treating autoimmune disorders, CCR1 is a top therapeutic target.
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| Cell Assay |
In summary, dermal microvascular endothelial cells cultured to confluence in Petri dishes are stimulated with IL-1β (10 ng/mL) for a duration of 12 hours, and immediately before the assay, they are pre-incubated with RANTES (10 nM) for 30 minutes at 37°C. The plates are mounted on the stage of an Olympus IMT-2 inverted microscope with ×20 and ×40 phase-contrast objectives, and they are assembled as the lower wall of a parallel wall flow chamber. Separated human blood monocytes are resuspended at a density of 5×105 cells/mL in assay buffer (HBSS) that has 0.5% human serum albumin, 10 mM HEPES, and a pH of 7.4. Addition of 1 mM Mg2+ and 1 mM Ca2+ occurs shortly before the assay. Cell suspensions are perfused into the flow chamber for five minutes at a rate of 1.5 dyn/cm2 while being maintained in a heating block at 37°C for the assay. Monocytes undergoing inhibition experiments are first preincubated for 10 minutes at 37°C with either a Me2SO control or BX471 at varying concentrations (0.1–10 μM). Expressed as cells/mm2, the number of firmLy adherent cells after 5 min is quantified in multiple fields (at least five per experiment) through image analysis using a JVC SR L 900 E video recorder and a long integration JVC 3CCD video camera. Primary adhesion, or the direct interactions between monocytes and endothelium, is the only type of adhesion that is examined.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C21H25CL2FN4O3
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| Molecular Weight |
471.35
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| Exact Mass |
434.15
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| Elemental Analysis |
C, 53.51; H, 5.35; Cl, 15.04; F, 4.03; N, 11.89; O, 10.18
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| CAS # |
288262-96-4
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| Related CAS # |
BX471; 217645-70-0
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| Appearance |
Solid powder
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| SMILES |
C[C@@H]1CN(CCN1C(=O)COC2=C(C=C(C=C2)Cl)NC(=O)N)CC3=CC=C(C=C3)F.Cl
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| InChi Key |
FRUCNQBAWUHKLS-PFEQFJNWSA-N
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| InChi Code |
InChI=1S/C21H24ClFN4O3.ClH/c1-14-11-26(12-15-2-5-17(23)6-3-15)8-9-27(14)20(28)13-30-19-7-4-16(22)10-18(19)25-21(24)29;/h2-7,10,14H,8-9,11-13H2,1H3,(H3,24,25,29);1H/t14-;/m1./s1
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| Chemical Name |
[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-2-oxoethoxy]phenyl]urea;hydrochloride
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (6.36 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 30.0 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: ≥ 3 mg/mL (6.36 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 30.0 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: ≥ 3 mg/mL (6.36 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 | 2.1216 mL | 10.6078 mL | 21.2157 mL | |
| 5 mM | 0.4243 mL | 2.1216 mL | 4.2431 mL | |
| 10 mM | 0.2122 mL | 1.0608 mL | 2.1216 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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