PLX5622 free base
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MedKoo CAT#: 555604

CAS#: 1303420-67-8 (free base)

Description: PLX5622 is a highly selective brain penetrant and oral active CSF1R inhibitor. PLX5622 has been shown to eliminate microglia from the brain, which can be sustained in wild-type and the Alzheimer's disease model mice (3xTg-AD model). In the AD model PLX5622 prevents microglial association with amyloid β plaques and improves cognition.


Chemical Structure

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PLX5622 free base
CAS# 1303420-67-8 (free base)

Theoretical Analysis

MedKoo Cat#: 555604
Name: PLX5622 free base
CAS#: 1303420-67-8 (free base)
Chemical Formula: C21H19F2N5O
Exact Mass: 395.1558
Molecular Weight: 395.41
Elemental Analysis: C, 63.79; H, 4.84; F, 9.61; N, 17.71; O, 4.05

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 free base;

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

InChi Key: NSMOZFXKTHCPTQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H19F2N5O/c1-12-5-17-14(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/h3-5,7-9,11H,6,10H2,1-2H3,(H,24,28)(H,25,26)

SMILES Code: CC1=CN=C2C(C(CC3=C(F)N=C(NCC4=CC(F)=CN=C4OC)C=C3)=CN2)=C1

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 is a highly selective brain penetrant CSF1R inhibitor with an Ki of 5.9 nM, for extended and specific microglial elimination.
In vitro activity: This study exposed mixed glial cultures to 10 μM PLX5622 starting immediately after cell extraction (“early treatment”) or starting at day in vitro 12 (“late treatment”) for two weeks thereafter (Fig. 1). The microglial number was reduced to 8% of the control number in the early treatment group (as judged by immunostaining for Iba1 (Fig. 1A)). In contrast, late treatment reduced the microglial cell number to 25% of the control (Fig. 1A). The formation of the astrocytic monolayer and the GFAP-staining was not affected by CSF-1 receptor inhibition (Fig. 1B). Reference: J Neurosci Methods. 2020 Feb 15;332:108537. https://pubmed.ncbi.nlm.nih.gov/31790710/
In vivo activity: Flow cytometry analysis of blood samples from 11-week-old CTRL (control)/PLX (PLX5622)-treated mice showed a significant reduction of Ly6Chi monocytes and an apparent although not significant reduction of Ly6Clow monocytes and macrophages (Sup Fig. 9A–C). Analysis of CTRL and PLX tumors showed a significant reduction in the percentage of CD45int TAMs (tumor-associated macrophages/microglia) and microglia-like TAMs among all immune cells and CD45int TAMs among the CD45+ CD11b+ Ly6G− population in the PLX-treated tumors, indicating functional CSF1R inhibition in the PLX-treated tumors (Fig. 5C–F; Sup Fig 10A–B). Furthermore, this study found a positive correlation between tumor growth and the percentage of CD45int TAMs and microglia-like TAMs in the PLX-treated tumors but not in the CTRL-treated tumors that all have a high percentage of TAMs (Sup Fig 11A–B). In contrast, 4 weeks of PLX treatment led to a significant increase of CD8+ cytotoxic T cells and a decrease of B cells among lymphocytes in tumors, although there was no correlation between tumor growth and the percentage of these two immune cells types (Fig. 5H–I, ,K;K; Sup Fig 11D–E). Thus, CSF1R inhibition changes the immune microenvironment in a specific way that reduces a subset of TAMs and B cells but increases cytotoxic T cells. Furthermore, the correlation seen between the percentage of TAMs in a tumor treated with PLX and tumor growth might explain the heterogeneity in PLX treatment response, further supporting that the TAMs are a key immune cell influencing tumor growth. Reference: Oncogene. 2021 Jan; 40(2): 396–407. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855734/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 30.0 75.87

Preparing Stock Solutions

The following data is based on the product molecular weight 395.41 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. 2. Cunyat F, Rainho JN, West B, Swainson L, McCune JM, Stevenson M. Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing. J Virol. 2016 Jun 24;90(14):6255-6262. doi: 10.1128/JVI.00231-16. PMID: 27122585; PMCID: PMC4936142. 3. Clayton K, Delpech JC, Herron S, Iwahara N, Ericsson M, Saito T, Saido TC, Ikezu S, Ikezu T. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model. Mol Neurodegener. 2021 Mar 22;16(1):18. doi: 10.1186/s13024-021-00440-9. Erratum in: Mol Neurodegener. 2021 Apr 14;16(1):24. PMID: 33752701; PMCID: PMC7986521. 4. Tan IL, Arifa RDN, Rallapalli H, Kana V, Lao Z, Sanghrajka RM, Sumru Bayin N, Tanne A, Wojcinski A, Korshunov A, Bhardwaj N, Merad M, Turnbull DH, Lafaille JJ, Joyner AL. CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model. Oncogene. 2021 Jan;40(2):396-407. doi: 10.1038/s41388-020-01536-0. Epub 2020 Nov 6. PMID: 33159168; PMCID: PMC7855734.
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. 2. Cunyat F, Rainho JN, West B, Swainson L, McCune JM, Stevenson M. Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing. J Virol. 2016 Jun 24;90(14):6255-6262. doi: 10.1128/JVI.00231-16. PMID: 27122585; PMCID: PMC4936142.
In vivo protocol: 1. Clayton K, Delpech JC, Herron S, Iwahara N, Ericsson M, Saito T, Saido TC, Ikezu S, Ikezu T. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model. Mol Neurodegener. 2021 Mar 22;16(1):18. doi: 10.1186/s13024-021-00440-9. Erratum in: Mol Neurodegener. 2021 Apr 14;16(1):24. PMID: 33752701; PMCID: PMC7986521. 2. Tan IL, Arifa RDN, Rallapalli H, Kana V, Lao Z, Sanghrajka RM, Sumru Bayin N, Tanne A, Wojcinski A, Korshunov A, Bhardwaj N, Merad M, Turnbull DH, Lafaille JJ, Joyner AL. CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model. Oncogene. 2021 Jan;40(2):396-407. doi: 10.1038/s41388-020-01536-0. Epub 2020 Nov 6. PMID: 33159168; PMCID: PMC7855734.

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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.