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PLX5622 hemifumarate

Alias: PLX5622; PLX-5622; PLX 5622; PLX5622 hemifumarate;
Cat No.:V76619 Purity: ≥98%
PLX5622 hemifumarate is a selective, BBB (blood-brain barrier) permeable (penetrable), orally bioactive CSF1R inhibitor (antagonist) with IC50 of 0.016 µM and a Ki of 5.9 nM.
PLX5622 hemifumarate
PLX5622 hemifumarate Chemical Structure Product category: Others 13
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
10mg
50mg
Other Sizes

Other Forms of PLX5622 hemifumarate:

  • PLX5622 fumarate
  • PLX-5622
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description
PLX5622 hemifumarate is a selective, BBB (blood-brain barrier) permeable (penetrable), orally bioactive CSF1R inhibitor (antagonist) with IC50 of 0.016 µM and a Ki of 5.9 nM. It can be used before and during the course of the disease, expanded and specific Elimination of microglia. PLX5622 hemifumarate has good bioactivities.
Biological Activity I Assay Protocols (From Reference)
Targets
CSF1R[1]
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].
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.
References

[1]. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model. Nat Commun. 2019 Aug 21;10(1):3758.

[2]. Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain. Mol Pain. 2018 Jan-Dec;14:1744806918764979.

[3]. Concentration-dependent effects of CSF1R inhibitors on oligodendrocyte progenitor cells ex vivo and in vivo. Exp Neurol. 2019;318:32-41.

[4]. Negative feedback control of neuronal activity by microglia. Nature. 2020;586(7829):417-423.

[5]. Astrocytic response to neural injury is larger during development than in adulthood and is not predicated upon the presence of microglia, Brain, Behavior, & Immunity-Health, Volume 1, 2020, 100010, ISSN 2666-3546.

[6]. Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology. Brain. 2016;139(Pt 4):1265-1281.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C23H21F2N5O3
Exact Mass
395.16
Elemental Analysis
C, 60.92; H, 4.67; F, 8.38; N, 15.44; O, 10.58
Related CAS #
PLX5622;1303420-67-8
Appearance
Off-white to light yellow solid powder
Synonyms
PLX5622; PLX-5622; PLX 5622; PLX5622 hemifumarate;
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO :~100 mg/mL (~220.53 mM)
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.

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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.
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 corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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