Powder: -20°C for 3 years | In solvent: -80°C for 1 year
PLX5622 hemifumarate 是高度选择性的、能透过血脑屏障的、具有口服活性的 CSF1R 抑制剂,IC50值为 0.016 μM,Ki 值为 5.9 nM,可用于病程发展前和过程中,扩大和特异性的小胶质细胞的消除。PLX5622 hemifumarate 具有较理想的药代动力学特性。
产品描述 | PLX5622 hemifumarate is a highly selective brain penetrant and orally active CSF1R inhibitor with an IC 50 of 0.016 μM and Ki of 5.9 nM. PLX5622 hemifumarate allows for extended and specific microglial elimination, preceding and during pathology development. In vivo, PLX5622 hemifumarate demonstrates desirable PK properties in varies animals [1] [2]. |
体外活性 | PLX5622 (1-20 μM; 3 days) hemifumarate effectively depletes microglia while not affecting oligodendrocytes or astrocytes in cerebellar slices. PLX5622 (4 μM; 3 days) hemifumarate leads to a 30-40% reduction in NG2+ or PDGFRα+ cells, increasing to 90-95% at 20 μM. No reduction of NG2+ or PDGFRα+ OPCs is observed in slices exposed to 1 μM or 2 μM PLX5622 despite robust (~95%) depletion of the microglial cells [3]. |
体内活性 | Pharmacodynamics of PLX5622 hemifumarate in preclinical studies PLX5622 (1200 ppm; chow; for 3 weeks or 3 days; adult C57/Bl6 wild type mice) hemifumarate causes around 80% of microglia lost after 3 days of treatment and a 99% microglia loss after 3 weeks of treatment. PLX5622 (adult C57/Bl6 wild type mice aged 3 months; diet for 3 weeks) reduces microglia in cortex, striatum, cerebellum and hippocampus [4]. PLX5622 (50 mg/kg; intraperitoneal injection; once (neonatal rat) or twice (adult rat) a day; for a total of 14 days) hemifumarate depletes microglia by 80-90% within 3 days of treatment, which increases to > 90% by 7 days. After 14 days of PLX5622 treatment, microglia is depleted by > 96% in both neonates and adults while preserving baseline astrocyte quantity. (A single daily injection of 0.65% PLX5622 suspended in 5% dimethyl sulfoxide and 20% Kolliphor RH40 in 0.01 M PBS is sufficient for neonatal microglia depletion, adult depletion requires injections twice daily) [5]. PLX5622 (formulated in AIN-76A standard chow at 1200 mg/kg; for 28 days) hemifumarate leads to reduction in microglia throughout the CNS in 14-month-old 5xfAD mice [6]. Pharmacokinetics of PLX5622 hemifumarate in preclinical species [4] Species IV PO (gavage) Dose (mg/kg) AUC 0-∞ (ng hr/mL) CL (mL/min/kg) Vss (L/kg) t 1/2 (hr) Dose (mg/kg) AUC 0-∞ (ng hr/mL) Cmax (ng/mL) F Mouse 1.92 15,500 2.1 0.34 2.6 45 215,000 26,300 59% Rat (male) 1.13 2,630 7.7 1.2 2.3 45 99,600 12,000 95% Rat (female) 1.13 5,110 3.7 1.0 3.9 45 181,000 15,600 89% Dog 1.00 6,230 3.0 2.3 15 45 96,500 3,630 34% Monkey 1.35 2,100 11 1.6 2.2 ND ND ND ND Preparation of gavage dosing suspensions for PLX5622 hemifumarate [4] PLX5622 hemifumarate is dissolved in DMSO at a concentration that is 20x the final dosing solution. The compound stock is protected from light. A fresh stock is made each week. The components of the diluent generally are prepared a day or more in advance because they take time to dissolve completely: a) 2% hydroxypropyl methyl cellulose (HPMC): 2.0 g powder was brought to 100 mL deionized water; b) 25% Polysorbate 80 (PS80): 25 g was brought to 100 mL deionized water. To make 100 mL diluent, add 25 mL of 2% HPMC stock (0.5% final) and 4 mL of 25% PS80 stock (1% final) to 71 mL deionized water to have final 100 mL. Final composition after mixing with compound: 0.5% HPMC, 1% PS80, 5% DMSO. On each dosing day, the compound stock is diluted 20-fold as follows: 19 volumes of diluent are measured into the tube, and 1 volume of the 20x compound/DMSO stock is added. The cap is closed and the content of the tube is mixed by inversion and placed in a sonicating water bath to make a uniform suspension. |
分子量 | 453.45 |
分子式 | C25H23F2N5O5 |
CAS No. | T12505 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 100 mg/mL (220.53 mM), sonification is recommended.
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.2053 mL | 11.0266 mL | 22.0531 mL | 55.1329 mL |
5 mM | 0.4411 mL | 2.2053 mL | 4.4106 mL | 11.0266 mL | |
10 mM | 0.2205 mL | 1.1027 mL | 2.2053 mL | 5.5133 mL | |
20 mM | 0.1103 mL | 0.5513 mL | 1.1027 mL | 2.7566 mL | |
50 mM | 0.0441 mL | 0.2205 mL | 0.4411 mL | 1.1027 mL | |
100 mM | 0.0221 mL | 0.1103 mL | 0.2205 mL | 0.5513 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
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