PLX5622

PLX5622 is a highly selective brain penetrant and orally active CSF1R inhibitor (IC50=0.016 µM; Ki=5.9 nM). PLX5622 allows for extended and specific microglial elimination, preceding and during pathology development. PLX5622 demonstrates desirable PK properties in varies animals.

Product information

CAS Number: 1303420-67-8

Molecular Weight: 395.41

Formula: C21H19F2N5O

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

Smiles: CC1C=C2C(NC=C2CC2=CC=C(NCC3=CC(F)=CN=C3OC)N=C2F)=NC=1

InChiKey: NSMOZFXKTHCPTQ-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : ≥ 260 mg/mL (657.55 mM). H2O : < 0.1 mg/mL (insoluble).

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

How to use

In Vitro:

PLX5622 (1-20 μM; 3 days) effectively depletes microglia without affecting oligodendrocytes or astrocytes in cerebellar slices. PLX5622 (4 μM; 3 days) causes a 30-40% reduction in NG2+ or PDGFRα+ cells, and this increased to 90-95% at 20 μM. No reduction of NG2+ or PDGFRα+ OPCs is observed in slices exposed to 1 μM or 2 μM PLX5622 despite robust (~95%) depletion of the microglial cells.

In Vivo:

Pharmacodynamics of PLX5622 in preclinical studies PLX5622 (1200 ppm; chow; for 3 weeks or 3 days; adult C57/Bl6 wild type mice) leads to around 80% of microglia lost after 3 days of treatment and a 99% microglia loss after 3 weeks of treatment. PLX5622 (adult C57/Bl6 wild type mice aged 3 months; diet for 3 weeks) decreases microglia in cortex, striatum, cerebellum and hippocampus. PLX5622 (50 mg/kg; intraperitoneal injection; once (neonatal rat) or twice (adult rat) a day; for a total of 14 days) depletes microglia by 80-90% within 3 days of treatment, which increases to > 90% by 7 days. After 14 days of PLX5622 treatment, microglia is depleted by > 96% in both neonates and adults while preserving baseline astrocyte quantity. (A single daily injection of 0.65% PLX5622 suspended in 5% dimethyl sulfoxide and 20% Kolliphor RH40 in 0.01 M PBS is sufficient for neonatal microglia depletion, adult depletion requires injections twice daily). PLX5622 (formulated in AIN-76A standard chow at 1200 mg/kg; for 28 days) leads to reduction in microglia throughout the CNS in 14-month-old 5xfAD mice. Pharmacokinetics of PLX5622 in preclinical species

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