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PLX5622
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PLX5622图片
CAS NO:1303420-67-8
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
PLX5622 是高度选择性的、能透过血脑屏障的、口服有效的CSF1R抑制剂 (IC50= 0.016 μM;Ki= 5.9 nM),可用于病程发展前和过程中,扩大的和特异性的小胶质细胞的消除。PLX5622 具有较好的药理学特性。
生物活性

PLX5622 is a highly selective brain penetrant and orally activeCSF1Rinhibitor (IC50=0.016 μM;Ki=5.9 nM). PLX5622 allows for extended and specific microglial cells elimination, preceding and during pathology development. PLX5622 demonstrates desirable PK properties in variesanimals[1][2].

IC50& Target

IC50: 0.016 μM (CSF1R); Ki: 5.9 nM (CSF1R)[1][2]

体外研究
(In Vitro)

PLX5622 (1-20 μM; 3 days) effectively depletes microglia without affecting oligodendrocytes or astrocytes in cerebellar slices. PLX5622 (4 μM; 3 days) causes a 30-40% reduction in NG2+ or PDGFRα+ cells, and this increased 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].

体内研究
(In Vivo)

Pharmacodynamics of PLX5622 in preclinical studies
PLX5622 (1200 ppm; chow; for 3 weeks or 3 days; adult C57/Bl6 wild type mice) leads to 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) decreases 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) 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) leads to reduction in microglia throughout the CNS in 14-month-old 5xfAD mice[6].

Pharmacokinetics of PLX5622 in preclinical species[1]

SpeciesIVPO (gavage)
Dose
(mg/kg)
AUC0-∞
(ngohr/mL)
CL
(mL/min/kg)
Vss
(L/kg)
t1/2
(hr)
Dose
(mg/kg)
AUC0-∞
(ngohr/mL)
Cmax
(ng/mL)
F
Mouse1.9215,5002.10.342.645215,00026,30059%
Rat (male)1.132,6307.71.22.34599,60012,00095%
Rat (female)1.135,1103.71.03.945181,00015,60089%
Dog1.006,2303.02.3154596,5003,63034%
Monkey1.352,100111.62.2NDNDNDND

Preparation of gavage dosing suspensions for PLX5622[1]
PLX5622 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.

Clinical Trial
分子量

395.41

性状

Solid

Formula

C21H19F2N5O

CAS 号

1303420-67-8

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL(63.23 mM;ultrasonic and warming and heat to 80℃)

Ethanol : 3.33 mg/mL(8.42 mM;ultrasonic and warming and heat to 60℃)

H2O :< 0.1 mg/mL(insoluble)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.5290 mL12.6451 mL25.2902 mL
5 mM0.5058 mL2.5290 mL5.0580 mL
10 mM0.2529 mL1.2645 mL2.5290 mL
*

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
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 5% DMSO    95% (0.5% Hypromellose    1%Tween-80) (Note: To make 100 mL diluent (0.5% Hypromellose    1%Tween-80), add 25 mL of 2% Hypromellose stock and 4 mL of 25%Tween-80stock to 71 mL ddH2O)

    Solubility: 6.5 mg/mL (16.44 mM); Suspended solution; Need ultrasonic and warming

  • 2.

    请依序添加每种溶剂: 5% DMSO    95% (20% Ethoxylated hydrogenated castor oil in saline)

    Solubility: 5 mg/mL (12.65 mM); Clear solution; Need ultrasonic

  • 3.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 3.12 mg/mL (7.89 mM); Clear solution

    此方案可获得 ≥ 3.12 mg/mL (7.89 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 31.2 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 4.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: ≥ 2.5 mg/mL (6.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.32 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 5.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (6.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.32 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。