PLX5622 fumarate

• CAS: 2749102-07-4
• Catalog Number: ACM2749102074
• Category: Inhibitors
• Molecular Weight: 906.90
• Molecular Formula: C46H42F4N10O6
• 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%.
• Synonyms: PLX5622; PLX-5622; PLX 5622; PLX5622 fumarate
• IUPAC 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
• Canonical SMILES: 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
• InChI: 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+
• InChI Key: FMEISBYRQFIJPD-WXXKFALUSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1303420-67-8 (free base); 2743279-01-6 (HCl); 2749102-07-4 (fumarate)
• Biological Target: PLX5622 fumarate is a CSF1R inhibitor with a Ki of 5.9 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 60.92; H, 4.67; F, 8.38; N, 15.44; O, 10.58
• Exact Mass: 395.1558
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).