PLX5622 hemifumarate
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MedKoo CAT#: 555654

CAS#: PLX5622 hemifumarate

Description: PLX5562 is a highly selective brain-penetrant CSF1R inhibitor. In the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Microglia appear to contribute to multiple facets of AD etiology – microglia appear crucial to the initial appearance and structure of plaques, and following plaque formation, promote a chronic inflammatory state modulating neuronal gene expression changes in response to Aβ/AD pathology. PLX5622 demonstrated desirable PK properties in mice, rats, dogs, and monkeys with a brain penetrance of ~20%.


Chemical Structure

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PLX5622 hemifumarate
CAS# PLX5622 hemifumarate

Theoretical Analysis

MedKoo Cat#: 555654
Name: PLX5622 hemifumarate
CAS#: PLX5622 hemifumarate
Chemical Formula: C46H42F4N10O6
Exact Mass: 395.1558
Molecular Weight: 906.9
Elemental Analysis: C, 60.92; H, 4.67; F, 8.38; N, 15.44; O, 10.58

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 5250.0 Ready to ship
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Related CAS #: 1303420-67-8 (free base)   2743279-01-6 (HCl)   2749102-07-4 (fumarate)   PLX5622 hemifumarate  

Synonym: PLX5622; PLX-5622; PLX 5622; PLX5622 hemifumarate;

IUPAC/Chemical Name: 6-fluoro-N-((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine hemifumarate

InChi Key: FMEISBYRQFIJPD-WXXKFALUSA-N

InChi Code: InChI=1S/2C21H19F2N5O.C4H4O4/c2*1-12-5-17-14(9-26-20(17)25-8-12)6-13-3-4-18(28-19(13)23)24-10-15-7-16(22)11-27-21(15)29-2;5-3(6)1-2-4(7)8/h2*3-5,7-9,11H,6,10H2,1-2H3,(H,24,28)(H,25,26);1-2H,(H,5,6)(H,7,8)/b;;2-1+

SMILES Code: CC1=CN=C(NC=C2CC3=C(F)N=C(NCC4=CC(F)=CN=C4OC)C=C3)C2=C1.O=C(O)/C=C/C(O)=O.CC5=CN=C(NC=C6CC7=C(F)N=C(NCC8=CC(F)=CN=C8OC)C=C7)C6=C5

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: PLX5622 fumarate is a CSF1R inhibitor with a Ki of 5.9 nM.
In vitro activity: The CSF-1R inhibitor PLX5622 was applied in primary mouse glial cultures and microglial dose-responses were analyzed, starting at different time-points and incubating for various periods of time. The application of 10 μM PLX5622 immediately after cell preparation depleted microglia to 8% at 1 week, to 2% at 4 weeks and to 0.5% at 6 weeks (half-time 3.5 days). When mixed glial cultures were treated with 10 μM PLX5622 starting at day in vitro 12, microglia depletion was slower (half-time 6 days) and not complete, indicating a decreased sensitivity to CSF-1. The remaining astrocytes preserved their proliferation ability, their migration in a scratch wound assay, and their pro-inflammatory (IL-6) response towards lipopolysaccharide. Reference: J Neurosci Methods. 2020 Feb 15;332:108537. https://www.sciencedirect.com/science/article/abs/pii/S0165027019303942?via%3Dihub
In vivo activity: 5xFAD mice, which exhibit plaque pathology from 3 months of age, underwent treatment at 1.5 months of age with PLX5622-formulated chow (1200 ppm) or control diet continuously for either 10–24 weeks. In the brain, 5xFAD mice displayed increased numbers of microglia/myeloid cells at both 4 and 7 months of age compared to wild-type mice, with masses of enlarged, plaque-associated cells seen throughout the brain (Fig. 3c). Oral PLX5622 treatment led to almost complete microglial elimination (97–100% reduction; Fig. 3c and quantified in e and f), even with 24 weeks of treatment, showing that PLX5622 allows for extended elimination of microglia. In the Morris water maze probe trial, PLX5622-treated wild-type mice tended to spend more time in the platform zone compared to wild-type mice (Fig. 3k), indicating that the long-term absence of microglia is not detrimental to murine cognitive function and may be beneficial, at least in this assay. Reference: Nat Commun. 2019 Aug 21;10(1):3758. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704256/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 110.3

Preparing Stock Solutions

The following data is based on the product molecular weight 906.9 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Hupp S, Iliev AI. CSF-1 receptor inhibition as a highly effective tool for depletion of microglia in mixed glial cultures. J Neurosci Methods. 2020 Feb 15;332:108537. doi: 10.1016/j.jneumeth.2019.108537. Epub 2019 Nov 29. PMID: 31790710.
In vitro protocol: 1. Hupp S, Iliev AI. CSF-1 receptor inhibition as a highly effective tool for depletion of microglia in mixed glial cultures. J Neurosci Methods. 2020 Feb 15;332:108537. doi: 10.1016/j.jneumeth.2019.108537. Epub 2019 Nov 29. PMID: 31790710.
In vivo protocol: 1. Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, Zhang Y, Spevak W, Lin J, Phan NY, Habets G, Rymar A, Tsang G, Walters J, Nespi M, Singh P, Broome S, Ibrahim P, Zhang C, Bollag G, West BL, Green KN. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model. Nat Commun. 2019 Aug 21;10(1):3758. doi: 10.1038/s41467-019-11674-z. PMID: 31434879; PMCID: PMC6704256. 2. Ali S, Mansour AG, Huang W, Queen NJ, Mo X, Anderson JM, Hassan QN 2nd, Patel RS, Wilkins RK, Caligiuri MA, Cao L. CSF1R inhibitor PLX5622 and environmental enrichment additively improve metabolic outcomes in middle-aged female mice. Aging (Albany NY). 2020 Feb 2;12(3):2101-2122. doi: 10.18632/aging.102724. Epub 2020 Feb 2. PMID: 32007953; PMCID: PMC7041757.

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1: Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, Zhang Y, Spevak W, Lin J, Phan NY, Habets G, Rymar A, Tsang G, Walters J, Nespi M, Singh P, Broome S, Ibrahim P, Zhang C, Bollag G, West BL, Green KN. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model. Nat Commun. 2019 Aug 21;10(1):3758. doi: 10.1038/s41467-019-11674-z. PubMed PMID: 31434879; PubMed Central PMCID: PMC6704256.

2: Hutchinson JM, Isaacson LG. Elimination of microglia in mouse spinal cord alters the retrograde CNS plasticity observed following peripheral axon injury. Brain Res. 2019 Oct 15;1721:146328. doi: 10.1016/j.brainres.2019.146328. Epub 2019 Jul 8. PubMed PMID: 31295468.

3: Todd L, Palazzo I, Suarez L, Liu X, Volkov L, Hoang TV, Campbell WA, Blackshaw S, Quan N, Fischer AJ. Reactive microglia and IL1β/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina. J Neuroinflammation. 2019 Jun 6;16(1):118. doi: 10.1186/s12974-019-1505-5. PubMed PMID: 31170999; PubMed Central PMCID: PMC6555727.

4: Garcia-Agudo LF, Janova H, Sendler LE, Arinrad S, Steixner AA, Hassouna I, Balmuth E, Ronnenberg A, Schopf N, van der Flier FJ, Begemann M, Martens H, Weber MS, Boretius S, Nave KA, Ehrenreich H. Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion. FASEB J. 2019 Jul;33(7):8634-8647. doi: 10.1096/fj.201900337R. Epub 2019 May 15. PubMed PMID: 31090455.

5: Lehmann ML, Weigel TK, Poffenberger CN, Herkenham M. The Behavioral Sequelae of Social Defeat Require Microglia and Are Driven by Oxidative Stress in Mice. J Neurosci. 2019 Jul 10;39(28):5594-5605. doi: 10.1523/JNEUROSCI.0184-19.2019. Epub 2019 May 13. PubMed PMID: 31085604; PubMed Central PMCID: PMC6616288.

6: Liu Y, Given KS, Dickson EL, Owens GP, Macklin WB, Bennett JL. Concentration-dependent effects of CSF1R inhibitors on oligodendrocyte progenitor cells ex vivo and in vivo. Exp Neurol. 2019 Aug;318:32-41. doi: 10.1016/j.expneurol.2019.04.011. Epub 2019 Apr 25. PubMed PMID: 31029597; PubMed Central PMCID: PMC6615458.

7: Kyle J, Wu M, Gourzi S, Tsirka SE. Proliferation and Differentiation in the Adult Subventricular Zone Are Not Affected by CSF1R Inhibition. Front Cell Neurosci. 2019 Apr 2;13:97. doi: 10.3389/fncel.2019.00097. eCollection 2019. PubMed PMID: 31001085; PubMed Central PMCID: PMC6454047.

8: Striebel JF, Race B, Williams K, Carroll JA, Klingeborn M, Chesebro B. Microglia are not required for prion-induced retinal photoreceptor degeneration. Acta Neuropathol Commun. 2019 Mar 25;7(1):48. doi: 10.1186/s40478-019-0702-x. PubMed PMID: 30909963; PubMed Central PMCID: PMC6432762.

9: Sanchez JMS, DePaula-Silva AB, Doty DJ, Truong A, Libbey JE, Fujinami RS. Microglial cell depletion is fatal with low level picornavirus infection of the central nervous system. J Neurovirol. 2019 Jun;25(3):415-421. doi: 10.1007/s13365-019-00740-3. Epub 2019 Mar 11. PubMed PMID: 30859497; PubMed Central PMCID: PMC6635090.

10: Yi SY, Barnett BR, Torres-Velázquez M, Zhang Y, Hurley SA, Rowley PA, Hernando D, Yu JJ. Detecting Microglial Density With Quantitative Multi-Compartment Diffusion MRI. Front Neurosci. 2019 Feb 19;13:81. doi: 10.3389/fnins.2019.00081. eCollection 2019. PubMed PMID: 30837826; PubMed Central PMCID: PMC6389825.

11: Zhan L, Krabbe G, Du F, Jones I, Reichert MC, Telpoukhovskaia M, Kodama L, Wang C, Cho SH, Sayed F, Li Y, Le D, Zhou Y, Shen Y, West B, Gan L. Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain. PLoS Biol. 2019 Feb 8;17(2):e3000134. doi: 10.1371/journal.pbio.3000134. eCollection 2019 Feb. PubMed PMID: 30735499; PubMed Central PMCID: PMC6383943.

12: Funk KE, Klein RS. CSF1R antagonism limits local restimulation of antiviral CD8(+) T cells during viral encephalitis. J Neuroinflammation. 2019 Jan 31;16(1):22. doi: 10.1186/s12974-019-1397-4. PubMed PMID: 30704498; PubMed Central PMCID: PMC6354430.

13: Carroll JA, Chesebro B. Neuroinflammation, Microglia, and Cell-Association during Prion Disease. Viruses. 2019 Jan 15;11(1). pii: E65. doi: 10.3390/v11010065. Review. PubMed PMID: 30650564; PubMed Central PMCID: PMC6356204.

14: Sawicki CM, Kim JK, Weber MD, Faw TD, McKim DB, Madalena KM, Lerch JK, Basso DM, Humeidan ML, Godbout JP, Sheridan JF. Microglia Promote Increased Pain Behavior through Enhanced Inflammation in the Spinal Cord during Repeated Social Defeat Stress. J Neurosci. 2019 Feb 13;39(7):1139-1149. doi: 10.1523/JNEUROSCI.2785-18.2018. Epub 2018 Dec 17. PubMed PMID: 30559153; PubMed Central PMCID: PMC6381245.

15: Kokona D, Ebneter A, Escher P, Zinkernagel MS. Colony-stimulating factor 1 receptor inhibition prevents disruption of the blood-retina barrier during chronic inflammation. J Neuroinflammation. 2018 Dec 12;15(1):340. doi: 10.1186/s12974-018-1373-4. PubMed PMID: 30541565; PubMed Central PMCID: PMC6292111.

16: Weber MD, McKim DB, Niraula A, Witcher KG, Yin W, Sobol CG, Wang Y, Sawicki CM, Sheridan JF, Godbout JP. The Influence of Microglial Elimination and Repopulation on Stress Sensitization Induced by Repeated Social Defeat. Biol Psychiatry. 2019 Apr 15;85(8):667-678. doi: 10.1016/j.biopsych.2018.10.009. Epub 2018 Oct 25. PubMed PMID: 30527629; PubMed Central PMCID: PMC6440809.

17: O'Neil SM, Witcher KG, McKim DB, Godbout JP. Forced turnover of aged microglia induces an intermediate phenotype but does not rebalance CNS environmental cues driving priming to immune challenge. Acta Neuropathol Commun. 2018 Nov 26;6(1):129. doi: 10.1186/s40478-018-0636-8. PubMed PMID: 30477578; PubMed Central PMCID: PMC6260864.

18: Paschalis EI, Lei F, Zhou C, Kapoulea V, Dana R, Chodosh J, Vavvas DG, Dohlman CH. Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11359-E11368. doi: 10.1073/pnas.1807123115. Epub 2018 Nov 15. PubMed PMID: 30442669; PubMed Central PMCID: PMC6275537.

19: Witcher KG, Bray CE, Dziabis JE, McKim DB, Benner BN, Rowe RK, Kokiko-Cochran ON, Popovich PG, Lifshitz J, Eiferman DS, Godbout JP. Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation. Glia. 2018 Dec;66(12):2719-2736. doi: 10.1002/glia.23523. Epub 2018 Oct 30. PubMed PMID: 30378170.

20: Takeda A, Shinozaki Y, Kashiwagi K, Ohno N, Eto K, Wake H, Nabekura J, Koizumi S. Microglia mediate non-cell-autonomous cell death of retinal ganglion cells. Glia. 2018 Nov;66(11):2366-2384. doi: 10.1002/glia.23475. Epub 2018 Oct 29. PubMed PMID: 30375063.