Gamma-secretase
信号通路图
研究领域
- 抑制剂选择性比较
- 溶解性比较
| 目录号 | 产品目录 | 溶解度(25°C) | ||
|---|---|---|---|---|
| 水 | DMSO | 酒精 | ||
| S2215 | DAPT (GSI-IX) | <1 mg/mL | 86 mg/mL | 50 mg/mL |
| S1575 | RO4929097 | <1 mg/mL | 93 mg/mL | 16 mg/mL |
| S1594 | Semagacestat (LY450139) | <1 mg/mL | 72 mg/mL | 41 mg/mL |
| S2660 | MK-0752 | <1 mg/mL | 89 mg/mL | 45 mg/mL |
| S1262 | Avagacestat (BMS-708163) | <1 mg/mL | 104 mg/mL | <1 mg/mL |
| S2711 | Dibenzazepine (YO-01027) | <1 mg/mL | 92 mg/mL | <1 mg/mL |
| S2714 | LY411575 | <1 mg/mL | 95 mg/mL | 13 mg/mL |
| S8018 | Nirogacestat (PF-03084014, PF-3084014) | <1 mg/mL | 97 mg/mL | 97 mg/mL |
| S8280 | IMR-1 | <1 mg/mL | 70 mg/mL | <1 mg/mL |
| S7673 | L-685,458 | <1 mg/mL | 100 mg/mL | 6 mg/mL |
| S7399 | FLI-06 | <1 mg/mL | 88 mg/mL | 8 mg/mL |
| S7169 | Crenigacestat (LY3039478) | <1 mg/mL | 92 mg/mL | 71 mg/mL |
| S2215 | DAPT (GSI-IX) | <1 mg/mL | 86 mg/mL | 50 mg/mL |
| S1575 | RO4929097 | <1 mg/mL | 93 mg/mL | 16 mg/mL |
| S1594 | Semagacestat (LY450139) | <1 mg/mL | 72 mg/mL | 41 mg/mL |
| S2660 | MK-0752 | <1 mg/mL | 89 mg/mL | 45 mg/mL |
| S1262 | Avagacestat (BMS-708163) | <1 mg/mL | 104 mg/mL | <1 mg/mL |
| S2711 | Dibenzazepine (YO-01027) | <1 mg/mL | 92 mg/mL | <1 mg/mL |
| S2714 | LY411575 | <1 mg/mL | 95 mg/mL | 13 mg/mL |
| S8018 | Nirogacestat (PF-03084014, PF-3084014) | <1 mg/mL | 97 mg/mL | 97 mg/mL |
| S8280 | IMR-1 | <1 mg/mL | 70 mg/mL | <1 mg/mL |
| S7673 | L-685,458 | <1 mg/mL | 100 mg/mL | 6 mg/mL |
| S7399 | FLI-06 | <1 mg/mL | 88 mg/mL | 8 mg/mL |
| S7169 | Crenigacestat (LY3039478) | <1 mg/mL | 92 mg/mL | 71 mg/mL |
特异性亚型抑制剂
- Gamma-secretase抑制剂（24）
- 新Gamma-secretase产品
| 产品目录 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX)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。 |
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| S1575 |
RO4929097RO4929097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。 |
(d,e) Effect of TUG1 overexpression on Nestin activity. Plasmid vectors expressing indicated genes were added to GSC-pE-Nes-222 treated with RO4929097. Phase-contrast and Nestin-EGFP images were shown in (d). Scale bars, 100 μm. (e) Intensity of Nestin-EGFP (left) and number of viable cells (right) compared with the DMSO control were quantified. Viable cells were assessed by trypan blue staining. *P<0.01, Kruskal–Wallis analysis. For all the experimental data, error bars indicate +s.d. (n=3).
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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。 |
Cultures were assessed in A for TRAP by enzyme histochemistry 5-8 days following exposure to Rankl. Values are means ± S.D.; n = 6 for all data sets except for Notch2Q2319X DMSO at day 5 where n = 5; the right upper panel shows representative culture fields of TRAP-stained multinucleated cells 8 days after the addition of Rankl.
|
|
| 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。 |
Jurkat cells were treated with (D) TRAIL (20 ng/ml), MK-0752 (50 µM) or a combination of the two for 48 h. Vehicle control for (D), 0.1% (v/v) dimethyl sulfoxide. Data shown are the mean ± standard error of the mean of ≥3 independent experiments. *P≤0.05, **P≤0.01. TRAIL, tumour necrosis factor-related apoptosis-inducing ligand.
|
|
| 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)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。 |
NSG mice were engrafted with human DND41 cells in 3 independent experiments. After DBZ treatment, marrow leukemia burden was determined by the expression of human CD45 (hCD45). Host LSK (hCD45−) (A), OB (B) and MSC frequencies (C) were determined by FACS in control (receiving culture medium) or in xenografted mice treated with vehicle or DBZ (n=8–9.group).
|
|
| 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。 |
(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, PF-3084014)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。Phase 2。 |
(F) Tumour tissues were further analysed to detect the efficacy of the inhibitors by IHC staining using p-EGFR and Notch1. (4Fa) Notch1 staining was mostly confined on the cell membrane. (4Fc) After Erlotinib treatment, the Notch1 protein was cleaved and translocated to the nucleus. (4Fb) p-EGFR was overexpressed in the control group. (4Fd) Erlotinib treatment inhibited p-EGFR expression. (4Fe-f) PF-03084014 treatment reduced both Notch1 and p-EGFR expression. (4Fg-h) Synthetic therapy reduced the activation of Notch1 and EGFR pathway. Scale bar = 50 μm. *P < .05, **P < .01, ***P < .001
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| S8280 |
IMR-1IMR-1是靶向转录激活过程的新型Notch抑制剂，其IC50为26 μM。 |
||
| 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
|
|
| S7399 |
FLI-06FLI-06 是一种靶向Notch信号通路的新型抑制剂，EC50是2.3 μM。 |
G. In the presence of FLI-06, wound healing assay was conducted to evaluate the cell motility after transfection. Scale bar represents 200 μm. H. In the presence of FLI-06, invasion assay was conducted to evaluate the cell invasiveness after transfection. Data were from three independent experiments and were Mean ± SD. **p < 0.01 compared to cells transfected with vector, ##p < 0.01 compared to cells transfected with ACTG2. Scale bar represents 100 μm.
|
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| S7169 |
Crenigacestat (LY3039478)Crenigacestat (LY3039478)是一种有效的Notch抑制剂，IC50为0.41 nM。 |
||
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX)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。 |
|
|
| S1575 |
RO4929097RO4929097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。 |
(d,e) Effect of TUG1 overexpression on Nestin activity. Plasmid vectors expressing indicated genes were added to GSC-pE-Nes-222 treated with RO4929097. Phase-contrast and Nestin-EGFP images were shown in (d). Scale bars, 100 μm. (e) Intensity of Nestin-EGFP (left) and number of viable cells (right) compared with the DMSO control were quantified. Viable cells were assessed by trypan blue staining. *P<0.01, Kruskal–Wallis analysis. For all the experimental data, error bars indicate +s.d. (n=3).
|
|
| 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。 |
Cultures were assessed in A for TRAP by enzyme histochemistry 5-8 days following exposure to Rankl. Values are means ± S.D.; n = 6 for all data sets except for Notch2Q2319X DMSO at day 5 where n = 5; the right upper panel shows representative culture fields of TRAP-stained multinucleated cells 8 days after the addition of Rankl.
|
|
| 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。 |
Jurkat cells were treated with (D) TRAIL (20 ng/ml), MK-0752 (50 µM) or a combination of the two for 48 h. Vehicle control for (D), 0.1% (v/v) dimethyl sulfoxide. Data shown are the mean ± standard error of the mean of ≥3 independent experiments. *P≤0.05, **P≤0.01. TRAIL, tumour necrosis factor-related apoptosis-inducing ligand.
|
|
| 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)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。 |
NSG mice were engrafted with human DND41 cells in 3 independent experiments. After DBZ treatment, marrow leukemia burden was determined by the expression of human CD45 (hCD45). Host LSK (hCD45−) (A), OB (B) and MSC frequencies (C) were determined by FACS in control (receiving culture medium) or in xenografted mice treated with vehicle or DBZ (n=8–9.group).
|
|
| 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。 |
(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, PF-3084014)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。Phase 2。 |
(F) Tumour tissues were further analysed to detect the efficacy of the inhibitors by IHC staining using p-EGFR and Notch1. (4Fa) Notch1 staining was mostly confined on the cell membrane. (4Fc) After Erlotinib treatment, the Notch1 protein was cleaved and translocated to the nucleus. (4Fb) p-EGFR was overexpressed in the control group. (4Fd) Erlotinib treatment inhibited p-EGFR expression. (4Fe-f) PF-03084014 treatment reduced both Notch1 and p-EGFR expression. (4Fg-h) Synthetic therapy reduced the activation of Notch1 and EGFR pathway. Scale bar = 50 μm. *P < .05, **P < .01, ***P < .001
|
|
| S8280 |
IMR-1IMR-1是靶向转录激活过程的新型Notch抑制剂，其IC50为26 μM。 |
||
| 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
|
|
| S7399 |
FLI-06FLI-06 是一种靶向Notch信号通路的新型抑制剂，EC50是2.3 μM。 |
G. In the presence of FLI-06, wound healing assay was conducted to evaluate the cell motility after transfection. Scale bar represents 200 μm. H. In the presence of FLI-06, invasion assay was conducted to evaluate the cell invasiveness after transfection. Data were from three independent experiments and were Mean ± SD. **p < 0.01 compared to cells transfected with vector, ##p < 0.01 compared to cells transfected with ACTG2. Scale bar represents 100 μm.
|
|
| S7169 |
Crenigacestat (LY3039478)Crenigacestat (LY3039478)是一种有效的Notch抑制剂，IC50为0.41 nM。 |
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