Gamma-secretase
Signaling Pathway Map
Research Area
- Inhibitory Selectivity
- Solubility
| Catalog No. | Product Name | Solubility(25°C) | ||
|---|---|---|---|---|
| Water | DMSO | Alcohol | ||
| 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 |
| S7323 | CHF 5074 | <1 mg/mL | 59 mg/mL | 9 mg/mL |
| S8603 | NGP 555 | <1 mg/mL | 40 mg/mL | 3 mg/mL |
Isoform-specific Inhibitors
Gamma-secretase Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. |
|
|
| S1575 |
RO4929097RO4929097 is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. 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) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM in H4 human glioma cell. 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 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 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) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. 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) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively. |
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 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. |
(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) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2. |
The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
|
|
| S8280 |
IMR-1IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 26 μM. |
||
| S7673 |
L-685,458L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 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 is a novel inhibitor of Notch signaling with EC50 of 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) is an oral Notch inhibitor with an IC50 of 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).
|
|
| S7323New |
CHF 5074CHF5074 is a gamma-secretase modulator that reduces Aβ42 and Aβ40 secretion. The IC50s of CHF5074 for inhibition of COX-1 and COX-2 is above 100 μmol/L. |
||
| S8603 |
NGP 555NGP 555 is a small-molecule modulator of γ-secretase and has been successful in achieving good oral absorption, brain penetration, CNS activity, and specificity for a lipid-based membrane target preclinically. |
-J-Biol-Chem-20170119.gif)
-LY2811376-J-Biol-Chem-20150727.gif)
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. |
|
|
| S1575 |
RO4929097RO4929097 is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. 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) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM in H4 human glioma cell. 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 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 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) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. 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) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively. |
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 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. |
(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) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2. |
The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.
|
|
| S8280 |
IMR-1IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 26 μM. |
||
| S7673 |
L-685,458L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 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 is a novel inhibitor of Notch signaling with EC50 of 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) is an oral Notch inhibitor with an IC50 of 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).
|
-J-Biol-Chem-20170119.gif)
-LY2811376-J-Biol-Chem-20150727.gif)
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S7323New |
CHF 5074CHF5074 is a gamma-secretase modulator that reduces Aβ42 and Aβ40 secretion. The IC50s of CHF5074 for inhibition of COX-1 and COX-2 is above 100 μmol/L. |
||
| S8603 |
NGP 555NGP 555 is a small-molecule modulator of γ-secretase and has been successful in achieving good oral absorption, brain penetration, CNS activity, and specificity for a lipid-based membrane target preclinically. |
