JNJ-40418677

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.

No numbering system information yet

No physical and chemical property information yet

No production method and use information yet

No upstream information yet

No downstream information yet

No related product information yet