PLX5622 fumarate

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%.

Product information

CAS Number: 2749102-07-4

Molecular Weight: 906.88

Formula: C46H42F4N10O6

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

Smiles: CC1=CC2=C(NC=C2CC2=CC=C(NCC3=CC(F)=CN=C3OC)N=C2F)N=C1.CC1=CC2=C(NC=C2CC2=CC=C(NCC3=CC(F)=CN=C3OC)N=C2F)N=C1.OC(=O)/C=C/C(O)=O

InChiKey: FMEISBYRQFIJPD-WXXKFALUSA-N

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+

Technical Data

Appearance: Solid Power

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

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

References:

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.

Products are for research use only. Not for human use.