Edicotinib (JNJ-40346527) 是一种有效的、选择性的、具有血脑通透性和口服活性 CSF-1R 抑制剂，IC₅₀ 为 3.2 nM。Edicotinib 对 KIT 和 FLT3 的抑制作用较小，IC₅₀ 值分别为 20 nM 和 190 nM。Edicotinib 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。Edicotinib 可以用于阿尔茨海默病和类风湿性关节炎的研究。

Edicotinib (JNJ-40346527) is a potent, selective, brain penetrant and orally active colony-stimulating factor-1 receptor (CSF-1R) inhibitor with an IC 50 of 3.2 nM. Edicotinib exhibits less inhibitory effects on KIT and FLT3 with IC 50 values of 20 nM and 190 nM, respectively. Edicotinib limits microglial expansion and attenuates microglial proliferation and neurodegeneration in mice. Edicotinib has the potential for Alzheimer’s disease and rheumatoid arthritis research.

Solid

IC50: 3.2 nM (CSF-1R)
20 nM (KIT); 190 nM (FLT3)

Edicotinib (0.1 nM-1μM; 24 hours) Leads to a dose-dependent decrease of CSF1R activation and a concurrent reduction of ERK1 and ERK2 phosphorylation. The dose response curve shows the effect of JNJ-527 on CSF1R and ERK1/2, and the IC50 values are 18.6 nM and 22.5 nM for CSF1R and ERK1/2, respectively.
has not independently confirmed the accuracy of these methods. They are for reference only.Western Blot Analysis

Edicotinib (oral gavage; 3, 10, 30 and 100 mg/kg; 5 days) significantly inhibits microglial proliferation in ME7 mice. It diminishes the number of microglia (total CD45CD11b cells) only at the highest dose tested of 100 mg/kg, and JNJ-527 depletes up to 50% of patrolling blood monocytes at every dose tested (CD45CD11bLy6Ccells) with only a tendency for a reduction in the proportion of inflammatory monocytes (Ly6C high cells) at 100 mg/kg.
Edicotinib exhibits a good pharmacokinetic/pharmacodynamics (PK/PD) profile, the microglial proliferation data shows an EC 50 of 196/ml and 69 ng/g calculated from plasmatic and brain compound concentration, respectively.
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%.

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Powder -20°C 3 years；4°C 2 years

[1]. Mancuso R, et al. CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice.Brain. 2019 Oct 1;142(10):3243-3264.
[2]. Genovese MC, et al. Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy.J Rheumatol. 2015 Oct;42(10):1752-60.

In Vitro: DMSO : 16.67 mg/mL (36.11 mM; Need ultrasonic)配制储备液