Sulindac sulfide 是γ-secretase的一个非竞争性抑制剂,其对γ42-secretase的IC50值为20.2 μM。
靶点100 μM 的 Sulindac sulfide (SSide) 处理导致细胞死亡,推测是通过诱导凋亡引起。这不仅显著减少了Aβ的生成,还降低了总蛋白表达。Sulindac sulfide 对 Aβ42 分泌的IC50值为30.6±2.8 μM。而 SSone 和萘普生在100 μM浓度下对Aβ40或Aβ42分泌及Notch剪切无任何影响。
Sulindac sulfide 对γ42-secretase活性的抑制呈剂量依赖性,其IC50值为20.2±2.6 μM。酶反应速率与酶浓度曲线中斜率的减少表明,Sulindac sulfide 并非不可逆或伪不可逆抑制剂。此外,在CHAPSO缓冲液中预处理γ-secretase分解析出物后,再用不含 Sulindac sulfide 的 CHAPSO 缓冲液稀释并透析,γ-secretase活性几乎完全恢复。
综上所述,Sulindac sulfide 是 γ-secretase 复合体的真实分子靶标,并作为可逆的 γ-secretase 抑制剂发挥作用。
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
—— | Sulindac | 38194-50-2 | C20H17FO3S | 356.418 |
(R)-舒林酸 | (R)-sulindac | 190967-68-1 | C20H17FO3S | 356.418 |
(5-氟-2-甲基-1H-茚-3-基)乙酸 | 5-fluoro-2-methyl-1H-indene-3-acetic acid | 32004-66-3 | C12H11FO2 | 206.217 |
—— | ethyl 2-(5-fluoro-2-methyl-1H-inden-3-yl)acetate | 53077-50-2 | C14H15FO2 | 234.27 |
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
—— | sulindac sulfide methyl ester | 106647-49-8 | C21H19FO2S | 354.445 |
—— | Sulindac | 38194-50-2 | C20H17FO3S | 356.418 |
(R)-舒林酸 | (R)-sulindac | 190967-68-1 | C20H17FO3S | 356.418 |
(S)-舒林酸 | (S)-Sulindac sulfoxide | 149116-77-8 | C20H17FO3S | 356.418 |
硬树脂 | sulindac | 32004-68-5 | C20H17FO3S | 356.418 |
—— | sulindac sulfide ethyl ester | 1278488-69-9 | C22H21FO2S | 368.472 |
2-[(3Z)-6-氟-2-甲基-3-[(4-甲基磺酰基苯基)亚甲基]茚-1-基]乙酸 | sulindac sulfone | 59973-80-7 | C20H17FO4S | 372.417 |
—— | (Z)-4-hydroxybutyl 5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-ylacetate | 1538580-44-7 | C24H25FO3S | 412.525 |
—— | (Z)-5-fluoro-3-(2-hydroxyethyl)-2-methyl-1-(4-methylthiobenzylidene)indene | 141741-19-7 | C20H19FOS | 326.435 |
—— | (Z)-2-(nitrooxy)ethyl 2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetate | 1538580-30-1 | C22H20FNO5S | 429.469 |
—— | (Z)-4-(nitrooxy)butyl 2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetate | 1538580-29-8 | C24H24FNO5S | 457.523 |
—— | (Z)-6-(nitrooxy)hexyl 2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetate | 1538580-31-2 | C26H28FNO5S | 485.576 |
—— | (Z)-3-(nitrooxy)-2,2-bis((nitrooxy)methyl)propyl 5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-ylacetate | 1538580-33-4 | C25H24FN3O11S | 593.543 |
—— | (Z)-1,3-bis(nitrooxy)propan-2-yl 2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetate | 1538580-32-3 | C23H21FN2O8S | 504.493 |
—— | (Z)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)ethanamine | 1402045-01-5 | C20H20FNS | 325.45 |
—— | (Z)-N-(3-(dimethylamino)propyl)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetamide | —— | C25H29FN2OS | 424.582 |
—— | (Z)-N-ethyl-N-(3-(ethylamino)propyl)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetamide | —— | C27H33FN2OS | 452.636 |
—— | (Z)-N-(4-(dimethylamino)phenyl)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetamide | 944159-31-3 | C28H27FN2OS | 458.6 |
—— | (Z)-N-(4-(dimethylamino)benzyl)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetamide | 944159-27-7 | C29H29FN2OS | 472.626 |
—— | (Z)-2-amino-N-(2-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)-N-methylacetamido)ethyl)-N,3-dimethylbutanamide | —— | C29H36FN3O2S | 509.688 |
—— | (Z)-2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)-N-methyl-N-(2-(methylamino)ethyl)propanamide | —— | C25H29FN2OS | 424.582 |
—— | (Z)-5-fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylmethyl isocyanate | 141741-22-2 | C20H16FNOS | 337.418 |
—— | (Z)-4-(4-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)butoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-57-2 | C32H29FN2O7S2 | 636.722 |
—— | (Z)-4-(2-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-55-0 | C30H25FN2O7S2 | 608.668 |
—— | (Z)-4-(3-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)propoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-56-1 | C31H27FN2O7S2 | 622.695 |
—— | (Z)-4-((6-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)hexyl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole2-oxide | 1538580-58-3 | C34H33FN2O7S2 | 664.776 |
—— | 4-(((Z)-4-(2-((Z)-5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)but-2-en-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-61-8 | C32H27FN2O7S2 | 634.706 |
—— | (Z)-4-((4-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)but-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-60-7 | C32H25FN2O7S2 | 632.69 |
—— | (Z)-4-(2-(2-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)ethoxy)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-59-4 | C32H29FN2O8S2 | 652.721 |
—— | (Z)-4-(3-(2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-63-0 | C34H25FN2O7S2 | 656.712 |
—— | (Z)-4-(3-((2-(5-fluoro-2-methyl-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetoxy)methyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1538580-62-9 | C35H27FN2O7S2 | 670.739 |