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JNJ-40418677

CAS No. : 1146594-87-7

MCE 站：JNJ-40418677

产品活性：JNJ-40418677 是一种具有口服活性的 γ-分泌酶调节剂，可通过血脑屏障。JNJ-40418677 抑制 Aβ42 淀粉样蛋白和 NS2B-NS3 蛋白酶，IC₅₀ 分别为 200 nM 和 3.9 μM。JNJ-40418677 表现出良好的生物耐受性，可用于阿尔茨海默症的研究。

研究领域：Neuronal Signaling  |  Stem Cell/Wnt

作用靶点：γ-secretase  |  Amyloid-β

In Vitro: JNJ-40418677 (0.2 nM-0.3 mM; 16 h) selectively reduces Aβ42 secretion in cell culture supernatants of human neuroblastoma cells with mean IC₅₀ of 200 nM ａnd (0.2 nM-0.3 mM; 48 h) of rat primary neurons with mean IC₅₀ of 185 nM.
JNJ-40418677 (10 μM, 100 μM; 18 h) does not inhibit Notch processing or (6 nM-20 μM; 18 h) not affect formation of other amyloid precursor protein cleavage (CTF-β, CTF-α) products, ａnd shows no inhibitory activity against COX-1/2 at a high concentration of 60 μM.
JNJ-40418677 suppresses ZIKV in human neuronal stem cells with an EC₅₀ value of 3.2 μM, ａnd inhibits ZIKV NS2B-NS3 protease with an IC₅₀ value of 3.9 μM.

In Vivo: JNJ-40418677 (10-300 mg/kg; p.o.) decreases Aβ42 brain levels in a dose-dependent manner 4 h after treatment, while increasing Aβ38 level in non-transgenic mouse brain.
JNJ-40418677 (30 mg/kg; p.o.; once) shows the mean brain ａnd plasma levels 4 h after single dose are both 17 μM, indicating good brain penetration in non-transgenic mouse brain.
JNJ-40418677 (20-120 mg/kg; p.o.; 7 months) has good biological tolerance with no adverse effects in a chronic treatment in Tg2576 mice.
JNJ-40418677 (20-120 mg/kg; p.o.; 7 months) decreases the plaque number ａnd the area occupied by plaques in Tg2576 mice dose-dependently.

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