Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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50mg |
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Other Sizes |
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Targets |
CSF1R[1]
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ln Vitro |
In cerebellar slices, PLX5622(1–20 μM; 3 days) hemifumarate efficiently depletes microglia while having no effect on oligodendrocytes or astrocytes. NG2+ or PDGFRα+ cells are reduced by 30–40% when exposed to PLX5622(4 μM; 3 days) hemifumarate; at 20 μM, this rose to 90–95%. Despite a robust (~95%) depletion of microglial cells, slices treated to 1 μM or 2 μM PLX5622 show no change in NG2+ or PDGFRα+ OPCs[3].
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ln Vivo |
Pharmacodynamics of PLX5622 hemifumarate in preclinical research In adult C57/Bl6 wild type mice, PLX5622 (1200 ppm; chow; for 3 weeks or 3 days) hemifumarate causes around 80% and 99% of microglia to be destroyed after 3 days of therapy, respectively. Microglia in the brain, striatum, cerebellum, and hippocampus are reduced in PLX5622 (adult C57/Bl6 wild type mice, 3 months old; fed for 3 weeks)[4]. Hemifumarate (PLX5622; 50 mg/kg; intraperitoneal injection; once daily for newborn rats, or twice daily for adult rats) depletes microglia by 80–90% during 3 days of treatment, and by 7 days, it has increased to > 90%. Following 14 days of PLX5622 treatment, both neonates and adults see a > 96% reduction in microglia while maintaining the number of astrocytes. (For neonatal microglia depletion, a single daily injection of 0.65% PLX5622 suspended in 5% dimethyl sulfoxide and 20% Kolliphor RH40 in 0.01 M PBS is sufficient; injections twice daily are needed for adult depletion)[5]. In 14-month-old 5xfAD mice, PLX5622 (formulated in AIN-76A normal chow at 1200 mg/kg; for 28 days) hemifumarate reduces microglia throughout the CNS[6]. Pharmacokinetics of PLX5622 hemifumarate in preclinical species[4] Species IV PO (gavage) Dose (mg/kg) AUC0-∞ (ng·hr/mL) CL (mL/min/kg) Vss (L/kg) t1/2 (hr ) Dose (mg/kg) AUC0-∞ (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 9 5%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 has light protection. Every week, a new stock is created. Due to its slow dissolution, the diluent's ingredients are typically prepared a day or more in advance: a) 2% hydroxypropyl methyl cellulose (HPMC): 2.0 g of powder was added to 100 mL of deionized water; b) 25% Polysorbate 80 (PS80): 25 g of powder was added to 100 mL of deionized water. Add 4 mL of 25% PS80 stock (1% final) and 25 mL of 2% HPMC stock (0.5% final) to 71 mL of deionized water to make a final 100 mL of diluent. Following compound mixing, the final composition is 0.5% HPMC, 1% PS80, and 5% DMSO. The compound stock is diluted 20 times on each dosage day in this manner: 19 volumes of diluent are measured into the tube, and 1 volume of the compound/DMSO stock (20x) is added. To create a homogenous suspension, the tube's contents are combined by inversion and then put in a sonicating water bath after the cap is closed.
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References |
Molecular Formula |
C23H21F2N5O3
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Exact Mass |
395.16
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Elemental Analysis |
C, 60.92; H, 4.67; F, 8.38; N, 15.44; O, 10.58
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Related CAS # |
PLX5622;1303420-67-8
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Appearance |
Off-white to light yellow solid powder
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Synonyms |
PLX5622; PLX-5622; PLX 5622; PLX5622 hemifumarate;
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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) |
DMSO :~100 mg/mL (~220.53 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (7.17 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 3.25 mg/mL (7.17 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 32.5 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: ≥ 3.25 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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.