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Purity: ≥98%
PLX5622 is a novel and highly selective CNS-penetrant CSF1R inhibitor, that has the potential to be used for extended and specific microglial elimination, preceding and during pathology development. Myeloid cells express a large number of risk genes for the development of Alzheimer's disease (AD) either exclusively or highly. The survival of microglia is reliant on the signalling mediated by the colony-stimulating factor 1 receptor (CSF1R).
| Targets |
CSF-1R (IC50 = 0.016 μM); FLT3 (IC50 = 0.39 μM); KIT (IC50 = 0.86 μM); AURKC (IC50 = 1 μM); KDR (IC50 = 1.1 μM)
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| ln Vitro |
PLX5622 (1–20 μM; 3 days) efficiently reduces microglia in cerebellar slices while having no effect on oligodendrocytes or astrocytes. After three days at 4 μM, NG2+ or PDGFRα+ cell counts are reduced by 30–40%, and at 20 μM, this number rises to 90–95%. Despite a robust (~95%) depletion of the microglial cells, slices exposed to 1 μM or 2 μM PLX5622 show no reduction of NG2+ or PDGFRα+ OPCs[3].
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| ln Vivo |
PLX5622 (1200 ppm; chow; for 3 weeks or 3 days; adult C57/Bl6 wild type mice) causes approximately 80% and 99% of microglia to be lost after 3 days and 3 weeks of treatment, respectively. The microglia in the cortex, striatum, cerebellum, and hippocampus are reduced in PLX5622 (adult C57/Bl6 wild type mice, 3 months old; fed for 3 weeks)[4].
In a total of 14 days, PLX5622 (50 mg/kg; intraperitoneal injection; once daily for neonatal rats, or twice daily for adult rats) reduces microglia by 80–90% in 3 days and by more than 90% in 7 days. Both adults and neonates experience a > 96% reduction in microglia after 14 days of PLX5622 treatment, while baseline astrocyte quantity is maintained. (Depleting microglia in neonates only requires a single daily injection of 0.65% PLX5622 suspended in 5% dimethyl sulfoxide and 20% Kolliphor RH40 in 0.01 M PBS; twice-daily injections are needed for adult depletion.)[5]. PLX5622 (formulated in AIN-76A standard chow at 1200 mg/kg; for 28 days) reduces microglia throughout the CNS in 14-month-old 5xfAD mice[6]. |
| References | |
| Additional Infomation |
PLX5622 is a highly selective brain penetrant and orally active CSF1R inhibitor. PLX5622 allows for extended and specific microglial cells elimination, preceding and during pathology development. PLX5622 demonstrates desirable PK properties in varies animals. PLX5622 is mostly used in the way of feed free diet.
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| Molecular Formula |
C21H19F2N5O
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|---|---|
| Molecular Weight |
395.4053
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| Exact Mass |
395.16
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| Elemental Analysis |
C, 63.79; H, 4.84; F, 9.61; N, 17.71; O, 4.05
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| CAS # |
1303420-67-8
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| Related CAS # |
PLX5622 hemifumarate
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| PubChem CID |
52936034
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| Appearance |
White to light yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
529
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WPOXAFXHRJYEIC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27ClN4O3/c1-28-8-6-15(7-9-28)13-31-22-12-19-17(11-21(22)30-3)23(26-14-25-19)27-20-10-16(29-2)4-5-18(20)24/h4-5,10-12,14-15H,6-9,13H2,1-3H3,(H,25,26,27)
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| Chemical Name |
N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
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| Synonyms |
PLX5622 free base; PLX-5622 free base; PLX 5622 free base;PLX5622; PLX-5622; PLX 5622
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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 |
| 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: 79~100 mg/mL (199.8~252.9 mM)
Ethanol: ~3.3 mg/mL (~8.4 mM) H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 6.5 mg/mL (16.44 mM) in 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% Tween80 + stock to 71 mL ddH2O) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
Solubility in Formulation 2: 5 mg/mL (12.65 mM) in 5% DMSO + 95% (20% Ethoxylated hydrogenated castor oil in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.12 mg/mL (7.89 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.32 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 25.0 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. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.32 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5290 mL | 12.6451 mL | 25.2902 mL | |
| 5 mM | 0.5058 mL | 2.5290 mL | 5.0580 mL | |
| 10 mM | 0.2529 mL | 1.2645 mL | 2.5290 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01282684 | Completed | Drug: PLX5622 Drug: Placebo |
Healthy | Plexxikon | January 2011 | Phase 1 |
| NCT01329991 | Completed | Drug: PLX5622 Drug: Placebo |
Rheumatoid Arthritis | Plexxikon | May 2011 | Phase 1 |
 Design and synthesis schematic of the CSF1R inhibitor PLX5622 for extended microglial elimination.
No detectable alterations in Aβ levels or APP processing with microglia elimination in 5xFAD mice.
Remaining plaque-forming microglia in the microdissected hippocampus exhibit a DAM expression profile.Nat Commun. 2019 Aug 21;10(1):3758. |
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 Extended elimination of microglia does not induce peripheral leukocyte or behavioral abnormalities.
Microglia facilitate plaque formation and compaction.
Microglia mediate downregulation of neuronal/plasticity genes in the hippocampus in response to AD pathology.Nat Commun. 2019 Aug 21;10(1):3758. |
 Long-term elimination of microglia in 5xFAD mice reduces plaque number and volume and is accompanied by cerebral amyloid angiopathy (CAA) onset.
Administration of an analogous CSF1R inhibitor, PLX3397 (75 ppm and 600 ppm), to 5xFAD mice.
Microglia seed plaques. All analyses listed in respective order for retrosplenial (RS) cortex, somatosensory (SS) cortex, and thalamus.Nat Commun. 2019 Aug |
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