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。
| 生物活性 | JNJ-40418677 is an orally active modulator ofγ-secretase, can cross the blood-brain barrier. JNJ-40418677 inhibitsAβ42andNS2B-NS3 protease, withIC50s 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]. |
| IC50& Target | IC50: 185 nM (rat Aβ42)[1]; 200 nM (human Aβ42)[2]; 3.9 μM (ZIKV NS2B-NS3 protease)[3] |
体外研究
(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 IC50of 200 nM and (0.2 nM-0.3 mM; 48 h) of rat primary neurons with mean IC50of 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 EC50value of 3.2 μM, and inhibits ZIKV NS2B-NS3 protease with an IC50value of 3.9 μM[3].
Western Blot Analysis[1] | Cell Line: | HEK293 cells | | Concentration: | 10 μM | | Incubation Time: | 18 h | | Result: | Resulted Aβ42 decreasing, Aβ38 increasing and Aβ40 levels remained unchanged. |
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体内研究
(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: | Non-transgenic mouse (6-month-old)[1] | | 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)[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
