Gamma-secretase
Signaling Pathway Map
Research Area
Inhibitory Selectivity
Isoform-specific Inhibitors
Gamma-secretase Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX, LY-374973) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. DAPT enhances the apoptosis of human tongue carcinoma cells and regulates autophagy. |
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) 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. |
|
|
| 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. |
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 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 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) 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%. |
|
| S7168New |
LY900009LY900009 is a potent Notch inhibitor with IC50 of 0.27 nM. |
||
| S7394New |
MDL-28170MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. MDL-28170 is also an inhibitor of γ-secretase. |
||
| S2711 |
Dibenzazepine (YO-01027)Dibenzazepine (YO-01027, DBZ) 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. |
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 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. LY411575 induces apoptosis. |
(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) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Nirogacestat (PF-03084014, PF-3084014) induces apoptosis. 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 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
|
|
| S8185 |
FPS-ZM1FPS-ZM1 is a blood-brain-barrier permeant, non-toxic, tertiary amide compound which is a high affinity RAGE-specific inhibitor, blocking Aβ binding to the V domain of RAGE. |
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) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch. |
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).
|
|
| S7323 |
Itanapraced (CHF 5074)Itanapraced (CHF 5074, CSP-1103) 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. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2215 |
DAPT (GSI-IX)DAPT (GSI-IX, LY-374973) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. DAPT enhances the apoptosis of human tongue carcinoma cells and regulates autophagy. |
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) 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. |
|
|
| 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. |
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 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 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) 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%. |
|
| S7168New |
LY900009LY900009 is a potent Notch inhibitor with IC50 of 0.27 nM. |
||
| S7394New |
MDL-28170MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. MDL-28170 is also an inhibitor of γ-secretase. |
||
| S2711 |
Dibenzazepine (YO-01027)Dibenzazepine (YO-01027, DBZ) 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. |
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 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. LY411575 induces apoptosis. |
(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) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Nirogacestat (PF-03084014, PF-3084014) induces apoptosis. 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 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
|
|
| S8185 |
FPS-ZM1FPS-ZM1 is a blood-brain-barrier permeant, non-toxic, tertiary amide compound which is a high affinity RAGE-specific inhibitor, blocking Aβ binding to the V domain of RAGE. |
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) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch. |
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).
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S7323 |
Itanapraced (CHF 5074)Itanapraced (CHF 5074, CSP-1103) 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. |
