JNJ-40418677 is an orally active modulator of γ-secretase , can cross the blood-brain barrier. JNJ-40418677 inhibits Aβ42 and NS2B-NS3 protease , with IC 50 s of 200 nM and 3.9 μM, respectively. JNJ-40418677 displays good biological tolerance, can be use for Alzheimer’s disease research. Form:Solid IC50& Target:IC50: 185 nM (rat Aβ42); 200 nM (human Aβ42); 3.9 μM (ZIKV NS2B-NS3 protease) 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 IC 50 of 200 nM and (0.2 nM-0.3 mM; 48 h) of rat primary neurons with mean IC 50 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 EC 50 value of 3.2 μM, and inhibits ZIKV NS2B-NS3 protease with an IC 50 value of 3.9 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: HEK293 cells Concentration: 10 μM Incubation Time: 18 h Result: Resulted Aβ42 decreasing, Aβ38 increasing and Aβ40 levels remained unchanged. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Non-transgenic mouse (6-month-old) Dosage: 10, 30, 100, 300 mg/kg Administration: Oral gavage; once Result: Reduced the Aβ42 brain levels dose-dependently, with 82%, 64%, 39%, and 31% at the doses of 10, 30, 100, 300 mg/kg, respectively. Animal Model: Tg2576 mice (6-month-old) Dosage: 20, 60, 120 mg/kg Administration: Oral gavage; 7 months Result: Exhibited well tolerated activity, without adverse effects on body weight. Showed no influence on the steady state levels of full-length APP, CTF-a, and CTF-b at a dosage of 120 mg/kg. Significantly reduced plaque area fraction and number of plaques.