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MedKoo Cat#: 555604 | Name: PLX5622 free base
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

PLX5622 free base
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

This product was removed for the commercial reasons.
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
More Info
PLX5622 Reduces Disease Severity in Lethal CNS Infection by Off-Target Inhibition of Peripheral Inflammatory Monocyte Production
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/
Solvent mg/mL mM comments
Solubility
DMSO 30.0 75.87
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.
1: Yang T, Tang Y, Liu X, Gong S, Yao E. Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function. IUBMB Life. 2024 Sep 2. doi: 10.1002/iub.2903. Epub ahead of print. PMID: 39223969. 2: Chen Y, He W, Qiu J, Luo Y, Jiang C, Zhao F, Wei H, Meng J, Long T, Zhang X, Yang L, Xu Q, Wang J, Zhang C. Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation. Cell Mol Biol Lett. 2024 Aug 28;29(1):114. doi: 10.1186/s11658-024-00634-1. PMID: 39198723; PMCID: PMC11360871. 3: Mendoza-Romero HN, Biddinger JE, Bedenbaugh MN, Simerly RB. Microglia are Required for Developmental Specification of AgRP Innervation in the Hypothalamus of Offspring Exposed to Maternal High Fat Diet During Lactation. bioRxiv [Preprint]. 2024 Aug 12:2024.08.12.607566. doi: 10.1101/2024.08.12.607566. PMID: 39185162; PMCID: PMC11343114. 4: Zhou L, Xu Z, Lu H, Cho H, Xie Y, Lee G, Ri K, Duh EJ. Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion. J Neuroinflammation. 2024 Aug 24;21(1):210. doi: 10.1186/s12974-024-03190-9. PMID: 39182142; PMCID: PMC11344463. 5: Mohamed SH, Vanhoffelen E, Shun Fu M, Hei Lau P, Hain S, Seldeslachts L, Cosway E, Anderson G, McCulloch L, Vande Velde G, Drummond RA. CSF1R inhibition by PLX5622 reduces pulmonary fungal infection by depleting MHCIIhi interstitial lung macrophages. Mucosal Immunol. 2024 Aug 20:S1933-0219(24)00088-6. doi: 10.1016/j.mucimm.2024.08.007. Epub ahead of print. PMID: 39168451. 6: Ayoub R, Yang S, Ji H, Fan L, De Michino S, Mabbott DJ, Nieman BJ. Brain volume and microglial density changes are correlated in a juvenile mouse model of cranial radiation and CSF1R inhibitor treatment. NMR Biomed. 2024 Aug 20:e5222. doi: 10.1002/nbm.5222. Epub ahead of print. PMID: 39164196. 7: Hatch K, Lischka F, Wang M, Xu X, Stimpson CD, Barvir T, Cramer NP, Perl DP, Yu G, Browne CA, Dickstein DL, Galdzicki Z. The role of microglia in neuronal and cognitive function during high altitude acclimatization. Sci Rep. 2024 Aug 16;14(1):18981. doi: 10.1038/s41598-024-69694-9. PMID: 39152179; PMCID: PMC11329659. 8: Profaci CP, Harvey SS, Bajc K, Zhang TZ, Jeffrey DA, Zhang AZ, Nemec KM, Davtyan H, O'Brien CA, McKinsey GL, Longworth A, McMullen TP, Capocchi JK, Gonzalez JG, Lawson DA, Arnold TD, Davalos D, Blurton-Jones M, Dabertrand F, Bennett FC, Daneman R. Microglia are not necessary for maintenance of blood- brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism. Neuron. 2024 Sep 4;112(17):2910-2921.e7. doi: 10.1016/j.neuron.2024.07.015. Epub 2024 Aug 13. PMID: 39142282. 9: Kodali M, Madhu LN, Somayaji Y, Attaluri S, Huard C, Panda PK, Shankar G, Rao S, Shuai B, Gonzalez JJ, Oake C, Hering C, Babu RS, Kotian S, Shetty AK. Residual Microglia Following Short-term PLX5622 Treatment in 5xFAD Mice Exhibit Diminished NLRP3 Inflammasome and mTOR Signaling, and Enhanced Autophagy. bioRxiv [Preprint]. 2024 Jul 16:2024.07.11.603157. doi: 10.1101/2024.07.11.603157. PMID: 39071343; PMCID: PMC11275929. 10: Craig GA, Ryan L, Thapar J, McNamara NB, Hoffmann A, Page D, Rose J, Cox SR, Miron VE. Reflective imaging of myelin integrity in the human and mouse central nervous systems. Front Cell Neurosci. 2024 Jul 10;18:1408182. doi: 10.3389/fncel.2024.1408182. PMID: 39049821; PMCID: PMC11266064. 11: Diemler CA, MacLean M, Heuer SE, Hewes AA, Marola OJ, Libby RT, Howell GR. Microglia depletion leads to increased susceptibility to ocular hypertension- dependent glaucoma. Front Aging Neurosci. 2024 Jul 2;16:1396443. doi: 10.3389/fnagi.2024.1396443. PMID: 39015474; PMCID: PMC11250491. 12: Brown TC, Crouse EC, Attaway CA, Oakes DK, Minton SW, Borghuis BG, McGee AW. Microglia are dispensable for experience-dependent refinement of mouse visual circuitry. Nat Neurosci. 2024 Aug;27(8):1462-1467. doi: 10.1038/s41593-024-01706-3. Epub 2024 Jul 8. PMID: 38977886. 13: Wickel J, Chung HY, Ceanga M, von Stackelberg N, Hahn N, Candemir Ö, Baade- Büttner C, Mein N, Tomasini P, Woldeyesus DM, Andreas N, Baumgarten P, Koch P, Groth M, Wang ZQ, Geis C. Repopulated microglia after pharmacological depletion decrease dendritic spine density in adult mouse brain. Glia. 2024 Aug;72(8):1484-1500. doi: 10.1002/glia.24541. Epub 2024 May 23. PMID: 38780213. 14: Xu Y, Tang L, Zhou C, Sun L, Hu Y, Zhang Z, Xia S, Bao X, Yang H, Xu Y. Inhibition of ADORA3 promotes microglial phagocytosis and alleviates chronic ischemic white matter injury. CNS Neurosci Ther. 2024 May;30(5):e14742. doi: 10.1111/cns.14742. PMID: 38715283; PMCID: PMC11076989. 15: Stewart AN, Bosse-Joseph CC, Kumari R, Bailey WM, Park KA, Slone VK, Gensel JC. Non-resolving neuroinflammation regulates axon regeneration in chronic spinal cord injury. bioRxiv [Preprint]. 2024 Apr 24:2024.04.19.590106. doi: 10.1101/2024.04.19.590106. PMID: 38712123; PMCID: PMC11071389. 16: Liu JA, Walker WH 2nd, Meléndez-Fernández OH, Bumgarner JR, Zhang N, Walton JC, Meares GP, DeVries AC, Nelson RJ. Dim light at night shifts microglia to a pro-inflammatory state after cerebral ischemia, altering stroke outcome in mice. Exp Neurol. 2024 Jul;377:114796. doi: 10.1016/j.expneurol.2024.114796. Epub 2024 Apr 25. PMID: 38677449. 17: Li Z, Yu S, Li L, Zhou C, Wang L, Tang S, Gu N, Zhang Z, Huang Z, Chen H, Tang W, Wang Y, Yang X, Sun X, Yan J. TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia. Clin Transl Med. 2024 Apr;14(4):e1665. doi: 10.1002/ctm2.1665. PMID: 38649789; PMCID: PMC11035381. 18: Wang M, Caryotakis SE, Smith GG, Nguyen AV, Pleasure DE, Soulika AM. CSF1R antagonism results in increased supraspinal infiltration in EAE. J Neuroinflammation. 2024 Apr 20;21(1):103. doi: 10.1186/s12974-024-03063-1. PMID: 38643194; PMCID: PMC11031888. 19: Huang J, Hu X, Chen Z, Ouyang F, Li J, Hu Y, Zhao Y, Wang J, Yao F, Jing J, Cheng L. Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord. J Neuroinflammation. 2024 Apr 10;21(1):88. doi: 10.1186/s12974-024-03089-5. PMID: 38600569; PMCID: PMC11005239. 20: Diemler CA, MacLean M, Heuer SE, Hewes AA, Marola OJ, Libby RT, Howell GR. Microglia Depletion leads to Increased Susceptibility to Ocular Hypertension- Dependent Glaucoma. bioRxiv [Preprint]. 2024 Mar 10:2024.03.05.583529. doi: 10.1101/2024.03.05.583529. Update in: Front Aging Neurosci. 2024 Jul 02;16:1396443. doi: 10.3389/fnagi.2024.1396443. PMID: 38496398; PMCID: PMC10942367.
https://www.biorxiv.org/content/10.1101/2024.07.11.603157v1.full 1. Kodali M, Madhu LN, Somayaji Y, Attaluri S, Huard C, Panda PK, Shankar G, Rao S, Shuai B, Gonzalez JJ, Oake C, Hering C, Babu RS, Kotian S, Shetty AK. Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy. Aging Cell. 2025 Feb;24(2):e14398. doi: 10.1111/acel.14398. Epub 2024 Nov 21. PMID: 39571180; PMCID: PMC11822669.