Edicotinib 是能够透过血脑屏障的、口服具有活性的、选择性的CSF-1R抑制剂 (IC50:3.2 nM)。它对 KIT (IC50:20 nM) 和 FLT3 (IC50:190 nM) 的抑制作用较小。它抑制小胶质细胞的扩张，减弱小胶质细胞的增殖和神经退行性变。它可用于研究阿尔茨海默病和类风湿性关节炎。

Edicotinib is a brain penetrant and orally active inhibitor of the colony-stimulating factor-1 receptor (IC50: 3.2 nM). It shows less inhibitory effects on KIT and FLT3 (IC50: 20 nM and 190 nM). It has the potential for Alzheimer's disease and rheumatoid arthritis treatment.

Edicotinib (0.1 nM-1μM; 24 hours) causes a dose-dependent decrease of CSF1R activation. Edicotinib (0.1 nM-1μM; 24 hours) lead to a concurrent reduction of ERK1 and ERK2 phosphorylation. The dose-response curve displays the effect of Edicotinib on CSF1R and ERK1/2 (IC50: 18.6 nM and 22.5 nM for CSF1R and ERK1/2) [1].

Edicotinib (oral gavage; 30 mg/kg; 33 days) significantly reduces the density of microglia in CA1 of the hippocampus of ME7-prion mice (PU.1+ cells) by up to 30%. And the expression of IL-1β is also reduced, however not other inflammatory cytokines. Edicotinib (oral gavage; 3, 10, 30, and 100 mg/kg; 5 days) obviously inhibits microglial proliferation in ME7 mice.?It reduces the number of microglia (total CD45+CD11b+ cells) only at the highest dose tested of 100 mg/kg. At every dose tested (CD45+CD11b high Ly6C intermediate/low cells), JNJ-527 depletes up to 50% of patrolling blood monocytes. Only a tendency for a reduction in the proportion of inflammatory monocytes (Ly6C high?cells) at 100 mg/kg [1]. Edicotinib displays a good pharmacokinetic/pharmacodynamics (PK/PD) profile, the microglial proliferation data shows an EC50 of 196/ml and 69 ng/g calculated from plasmatic and brain compound concentration, respectively [1].

1142363-52-7

C27H35N5O2

461.6

JNJ-40346527;JNJ-527

DMSO:15 mg/mL (32.4 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years