| Bioactivity | 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 IC50s of 200 nM and 3.9 μM, respectively. JNJ-40418677 displays good biological tolerance, can be use for Alzheimer’s disease research[1][2][3]. |
| Target | IC50: 185 nM (rat Aβ42); 200 nM (human Aβ42); 3.9 μM (ZIKV NS2B-NS3 protease) |
| Invitro | 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[1].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[1].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[3]. Western Blot Analysis[1] Cell Line: |
| 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[1].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[1].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[1].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[1]. Animal Model: |
| Name | JNJ-40418677 |
| CAS | 1146594-87-7 |
| Formula | C26H22F6O2 |
| Molar Mass | 480.44 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Van Broeck B, et al. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease. Br J Pharmacol. 2011 May;163(2):375-89. [2]. Harrie J.M. Gijsen, et al. Chapter Five - Secretase Inhibitors and Modulators as a Disease-Modifying Approach Against Alzheimer's Disease. Annu Rep Med Chem. 2012. 47:55-69. [3]. Samrat SK, et al. Antiviral Agents against Flavivirus Protease: Prospect and Future Direction. Pathogens. 2022 Feb 25;11(3):293. |
JNJ-40418677
CAS: 1146594-87-7 F: C26H22F6O2 W: 480.44
JNJ-40418677 is an orally active modulator of γ-secretase, can cross the blood-brain barrier. JNJ-40418677 inhibits Aβ
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