| 中文名称: | BX471 hydrochloride | ||||
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| 英文名称: | BX471 hydrochloride | ||||
| 别名: | ZK-811752 hydrochloride | ||||
| CAS No: | 288262-96-4 | 分子式: | C21H25Cl2FN4O3 | 分子量: | 471.35 |
| CAS No: | 288262-96-4 | ||||
| 分子式: | C21H25Cl2FN4O3 | ||||
| 分子量: | 471.35 | ||||
基本信息
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产品编号： |
B10865 |
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产品名称： |
BX471 hydrochloride |
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CAS: |
288262-96-4 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
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分子量： |
471.35 |
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化学名： |
ZK-811752 hydrochloride |
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Solubility (25°C)： |
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体外:
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DMSO |
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Ethanol |
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Water |
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体内(现配现用): |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
2.1216mL |
10.6078mL |
21.2157mL |
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5mM |
0.4243mL |
2.1216mL |
4.2431mL |
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10mM |
0.2122mL |
1.0608mL |
2.1216mL |
生物活性
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产品描述 |
一种有效的，选择性的，非肽段的CCR1拮抗剂，抑制人CCR1活性，Ki值为1nM，对其选择性是对CCR2，CCR5和CXCR4的250倍。 |
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靶点 |
MIP-1α-CCR1 1nM (Ki) |
RANTES-CCR1 2.8nM (Ki) |
MCP-3-CCR1 5.5nM (Ki) |
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体外研究 |
BX471 is a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca2+mobilization,increase in extracellular acidification rate,CD11b expression,and leukocyte migration.BX471 demonstrats a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors.BX471 is also able to displace 125I-MIP-1α/CCL3 binding to mouse CCR1 in a concentration-dependent manner with a Ki of 215±46nM.Increasing concentrations of BX471 inhibits the Ca2+ transients induced by MIP-1α/CCL3 in both human and mouse CCR1 with IC50 of 5.8±1nM and 198±7nM,respectively.BX471 (0.1-10μM) shows a dose-dependent inhibition of RANTES-mediated and shear-resistant adhesion on IL-1β-activated microvascular endothelium in shear flow in isolated blood monocytes.BX471 also inhibits the RANTES-mediated adhesion of T lymphocytes to activated endothelium. |
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体内研究 |
BX471 (4mg/kg,p.o.or i.v.) is orally active with a bioavailability of 60% in dogs.Furthermore,BX471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis.BX471 (20mg/kg,s.c.) reaches peak plasma levels of 9μM by around 30 minutes,and this rapidly declines to approximately 0.4μM after 2hours.From 4 to 8hours the drug plasma levels drops to 0.1μM or lower.Mice treated with 20mg/kg of BX471 for 10 days shows a reduction of interstitial CD45 positive leukocytes of approximately 55%. BX471 has a borderline significant effect on the number of CCR5-positive CD8 cells in the peripheral blood.BX471 reduces the amount of FSP1-positive cells by 65% in UUO kidneys as compared with vehicle control.Pretreatment witih BX471 reduces macrophage and neutrophil accumulation in kidney after ischemia-reperfusion injury. |
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推荐实验方法(仅供参考)
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细胞实验: |
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Briefly,dermal microvascular endothelial cells grown to confluence in Petri dishes are stimulated with IL-1β(10ng/mL) for 12h followed by pre-incubation with RANTES (10nM) for 30 min at 37℃ just prior to assay.The plates are assembled as the lower wall in a parallel wall flow chamber and mounted on the stage of an Olympus IMT-2 inverted microscope with ×20 and ×40 phase-contrast objectives.Isolated human blood monocytes are isolated and resuspended at 5×105 cells/mL in assay buffer (HBSS) containing 10mM HEPES,pH 7.4 and 0.5% human serum albumin.Shortly before the assay,1mM Mg2+ and 1mM Ca2+ are added.The cell suspensions are kept in a heating block at 37℃ during the assay and perfused into the flow chamber at a rate of 1.5 dyn/cm2 for 5 min.For inhibition experiments,monocytes are preincubated with BX471 at different concentrations (0.1-10μM) or a Me2SO control for 10 min at 37℃.The number of firmLy adherent cells after 5 min is quantitated in multiple fields (at least five per experiment) by analysis of images recorded with a long integration JVC 3CCD video camera and a JVC SR L 900 E video recorder and are expressed as cells/mm2.The type of adhesion analyzed is restricted to primary,i.e.direct interactions of monocytes with endothelium. |
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动物实验: |
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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 4mg/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 6h post-dosing.EDTA is used as an anticoagulant.The samples are centrifuged (1000×g for 10 min at 4℃),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 (4.6×250mm) following a short isocratic elution method (35% methanol,65% water containing 0.1% trifluoroacetic acid).The total column flow (1mL/min) is split post-column to infuse 50μL/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. |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
