Gamma-secretase
信号通路图
研究领域
抑制剂选择性比较
Gamma-secretase产品
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX, LY-374973) 是一种新型γ-secretase抑制剂，抑制 Aβ产生，在HEK 293细胞中IC50为20 nM。DAPT可促进人类舌癌细胞的凋亡并调节自噬。 |
Western blotting showing increased unconjugated SUMO1 levels in Notch1 ΔE cells treated with 10 uM DAPT for 3 days. Tubulin was used as a loading control.
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| S1575 |
RO4929097RO4929097 (RG-4733)是一种γ secretase抑制剂，无细胞试验中IC50为4 nM，抑制Aβ40和Notch的细胞加工，EC50分别为14 nM和5 nM。Phase 2。 |
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| S1594 |
Semagacestat (LY450139)Semagacestat (LY450139)是一种γ-分泌酶抑制剂，作用于Aβ42，Aβ40和Aβ38，IC50分别为10.9 nM，12.1 nM和12.0 nM，也抑制Notch信号通路，人神经胶质瘤细胞中IC50为14.1 nM。Phase 3。 |
HEK/APPswe cells were either left non-treated (-) or exposed to the γ-secretase inhibitor (GSI) semagacestat (+) for 19 h prior to cell harvesting and membrane preparation (Substrate accumulation). Exposure of cells with GSI prior to membrane preparation results in higher Aβ1-42 and Aβx-42 signals as compared to membranes derived from non-GSI treated cells. Direct addition of semagacestat to the membranes in the novo Aβ production assay inhibited Aβ production (Semagacestat (1 µM)). The amount of Aβx-42 is higher than Aβ1-42 suggesting that C83 is the major substrate for the Aβ42 signal detected. |
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| S2660 |
MK-0752MK-0752是一种适度有效的γ-secretase（γ-分泌酶）抑制剂，降低Aβ40产量，IC50为5 nM。Phase 1/2。 |
HES1 expression after treatment with clinically available GSIs R04929097, BMS-708163, LY450139, and MK-0752 as determined by qRT-PCR.
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| S1262 |
Avagacestat (BMS-708163)Avagacestat (BMS-708163)是口服生物有效的，选择性的γ-分泌酶抑制剂，作用于Aβ40和Aβ42时，IC50分别为0.3 nM和0.27 nM，比作用于Notch选择性高193倍。Phase 2。 |
A panel of GICs lines was treated with various concentrations of γ secretase inhibitors BMS-708163. Cells were treated with increasing concentrations of γ secretase inhibitors in triplicate wells for 72 hours, and cell viability was assessed by CellTiter-Blue assay as described in Materials and Methods. The results shown are of a single experiment with three independent replicates cell viability was measured by CellTiter-Blue assay. The graph depicts cell viability at 72 hours. Cell viability in the vehicle control was considered as to be 100%. |
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| S2711 |
Dibenzazepine (YO-01027)Dibenzazepine (YO-01027, DBZ)是一种二肽γ-secretase抑制剂，作用于APPL和Notch分裂， 无细胞试验中IC50分别为2.6 nM和2.9 nM。 |
Tumor spheres formation assay. Images were taken at 48 h after treating the cells with various formulations of YO (scale bar 100 um).
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| S2714 |
LY411575LY411575是一种有效的γ-secretase抑制剂，在表达APP或NΔE的HEK293细胞中IC50为0.078 nM/0.082 nM(基于膜/细胞)，也抑制Notch分裂，IC50为0.39 nM。LY411575 可诱导凋亡。 |
(E) Quantitation of lumen from A-D. (F) RNA isolated from 6d acini and expression of NOTCH1 measured by qRT-PCR in triplicate. P values are * <.01, *** <0.001.
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| S8018 |
Nirogacestat (PF-03084014)Nirogacestat (PF-03084014, PF-3084014) 是一种选择性gamma-secretase抑制剂，在无细胞试验中IC50为6.2 nM。Nirogacestat (PF-03084014, PF-3084014) 可诱导凋亡。Phase 2。 |
The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
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| S7673 |
L-685,458L-685,458 是一种beta PP gamma-secretase活性的特异性有效抑制剂，其Ki值为17 nM.。 |
The levels of Aβ produced by neuronal differentiated NSCs in response to vehicle (0.1% DMSO), 10μM BSI IV, 10μM L685,458, or the indicated compounds at 3μM or 10μM for 24hours
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| S7394 |
MDL-28170MDL-28170 (Calpain Inhibitor III) 是一种有效的、选择性的 calpain 的抑制剂，可在全身给药后穿透血脑屏障并抑制脑半胱氨酸蛋白酶的活性。MDL-28170 也是 γ-secretase 的抑制剂。 |
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| S8185 |
FPS-ZM1FPS-ZM1是一种能透过血脑障壁、无毒性、三级酰胺化合物。是RAGE的特异性抑制剂，抑制Aβ与RAGE的V区域结合。 |
FPS-ZM1 suppresses S100B promoted migration and invasion abilities. *P < 0.05, **P < 0.01 vs “CM” groups; &P < 0.05, &&P < 0.01 vs “S100B+FPS” groups. |
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| S7169 |
Crenigacestat (LY3039478)Crenigacestat (LY3039478) 是一种有效的Notch和 gamma-secretase 的抑制剂，其对Notch的IC50值为0.41 nM。 |
Effect of LY3039478 on Hes protein in SGC7901/DDP cells. A, Protein expression of Hes-1 by Western blot. B, Expression level of Hes-1 by Western blot experiment. (*p < 0.05 control with LY3039478 0 μmol/L group; **p < 0.01 control with LY3039478 0 μmol/L group).
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| S7323 |
Itanapraced (CHF 5074)Itanapraced (CHF 5074, CSP-1103) 是gamma-secretase调节剂，可减少Aβ42和Aβ40的分泌。它可抑制COX1和COX2，IC50大于100 μM。 |
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| S8603 |
NGP 555NGP 555是γ-secretase的小分子调节剂，在靶向脂质膜的临床前实验中，NGP 555具有良好的口服吸收率、大脑渗透性、中枢神经系统活性和特异性。 |
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX, LY-374973) 是一种新型γ-secretase抑制剂，抑制 Aβ产生，在HEK 293细胞中IC50为20 nM。DAPT可促进人类舌癌细胞的凋亡并调节自噬。 |
Western blotting showing increased unconjugated SUMO1 levels in Notch1 ΔE cells treated with 10 uM DAPT for 3 days. Tubulin was used as a loading control.
|
|
| S1575 |
RO4929097RO4929097 (RG-4733)是一种γ secretase抑制剂，无细胞试验中IC50为4 nM，抑制Aβ40和Notch的细胞加工，EC50分别为14 nM和5 nM。Phase 2。 |
|
|
| S1594 |
Semagacestat (LY450139)Semagacestat (LY450139)是一种γ-分泌酶抑制剂，作用于Aβ42，Aβ40和Aβ38，IC50分别为10.9 nM，12.1 nM和12.0 nM，也抑制Notch信号通路，人神经胶质瘤细胞中IC50为14.1 nM。Phase 3。 |
HEK/APPswe cells were either left non-treated (-) or exposed to the γ-secretase inhibitor (GSI) semagacestat (+) for 19 h prior to cell harvesting and membrane preparation (Substrate accumulation). Exposure of cells with GSI prior to membrane preparation results in higher Aβ1-42 and Aβx-42 signals as compared to membranes derived from non-GSI treated cells. Direct addition of semagacestat to the membranes in the novo Aβ production assay inhibited Aβ production (Semagacestat (1 µM)). The amount of Aβx-42 is higher than Aβ1-42 suggesting that C83 is the major substrate for the Aβ42 signal detected. |
|
| S2660 |
MK-0752MK-0752是一种适度有效的γ-secretase（γ-分泌酶）抑制剂，降低Aβ40产量，IC50为5 nM。Phase 1/2。 |
HES1 expression after treatment with clinically available GSIs R04929097, BMS-708163, LY450139, and MK-0752 as determined by qRT-PCR.
|
|
| S1262 |
Avagacestat (BMS-708163)Avagacestat (BMS-708163)是口服生物有效的，选择性的γ-分泌酶抑制剂，作用于Aβ40和Aβ42时，IC50分别为0.3 nM和0.27 nM，比作用于Notch选择性高193倍。Phase 2。 |
A panel of GICs lines was treated with various concentrations of γ secretase inhibitors BMS-708163. Cells were treated with increasing concentrations of γ secretase inhibitors in triplicate wells for 72 hours, and cell viability was assessed by CellTiter-Blue assay as described in Materials and Methods. The results shown are of a single experiment with three independent replicates cell viability was measured by CellTiter-Blue assay. The graph depicts cell viability at 72 hours. Cell viability in the vehicle control was considered as to be 100%. |
|
| S2711 |
Dibenzazepine (YO-01027)Dibenzazepine (YO-01027, DBZ)是一种二肽γ-secretase抑制剂，作用于APPL和Notch分裂， 无细胞试验中IC50分别为2.6 nM和2.9 nM。 |
Tumor spheres formation assay. Images were taken at 48 h after treating the cells with various formulations of YO (scale bar 100 um).
|
|
| S2714 |
LY411575LY411575是一种有效的γ-secretase抑制剂，在表达APP或NΔE的HEK293细胞中IC50为0.078 nM/0.082 nM(基于膜/细胞)，也抑制Notch分裂，IC50为0.39 nM。LY411575 可诱导凋亡。 |
(E) Quantitation of lumen from A-D. (F) RNA isolated from 6d acini and expression of NOTCH1 measured by qRT-PCR in triplicate. P values are * <.01, *** <0.001.
|
|
| S8018 |
Nirogacestat (PF-03084014)Nirogacestat (PF-03084014, PF-3084014) 是一种选择性gamma-secretase抑制剂，在无细胞试验中IC50为6.2 nM。Nirogacestat (PF-03084014, PF-3084014) 可诱导凋亡。Phase 2。 |
The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
|
|
| S7673 |
L-685,458L-685,458 是一种beta PP gamma-secretase活性的特异性有效抑制剂，其Ki值为17 nM.。 |
The levels of Aβ produced by neuronal differentiated NSCs in response to vehicle (0.1% DMSO), 10μM BSI IV, 10μM L685,458, or the indicated compounds at 3μM or 10μM for 24hours
|
|
| S7394 |
MDL-28170MDL-28170 (Calpain Inhibitor III) 是一种有效的、选择性的 calpain 的抑制剂，可在全身给药后穿透血脑屏障并抑制脑半胱氨酸蛋白酶的活性。MDL-28170 也是 γ-secretase 的抑制剂。 |
||
| S8185 |
FPS-ZM1FPS-ZM1是一种能透过血脑障壁、无毒性、三级酰胺化合物。是RAGE的特异性抑制剂，抑制Aβ与RAGE的V区域结合。 |
FPS-ZM1 suppresses S100B promoted migration and invasion abilities. *P < 0.05, **P < 0.01 vs “CM” groups; &P < 0.05, &&P < 0.01 vs “S100B+FPS” groups. |
|
| S7169 |
Crenigacestat (LY3039478)Crenigacestat (LY3039478) 是一种有效的Notch和 gamma-secretase 的抑制剂，其对Notch的IC50值为0.41 nM。 |
Effect of LY3039478 on Hes protein in SGC7901/DDP cells. A, Protein expression of Hes-1 by Western blot. B, Expression level of Hes-1 by Western blot experiment. (*p < 0.05 control with LY3039478 0 μmol/L group; **p < 0.01 control with LY3039478 0 μmol/L group).
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| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S7323 |
Itanapraced (CHF 5074)Itanapraced (CHF 5074, CSP-1103) 是gamma-secretase调节剂，可减少Aβ42和Aβ40的分泌。它可抑制COX1和COX2，IC50大于100 μM。 |
||
| S8603 |
NGP 555NGP 555是γ-secretase的小分子调节剂，在靶向脂质膜的临床前实验中，NGP 555具有良好的口服吸收率、大脑渗透性、中枢神经系统活性和特异性。 |
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