Gamma-secretase

Sigaling Pathway Map

Research Area

Inhibitory Selectivity

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Notes:
2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Isoform-specific Inhibitors

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

RO4929097

RO4929097 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.

S2660

MK-0752

MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.

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.

S7169New

LY3039478

LY3039478 is a novel and orally bioavailable inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with IC50 of ~1 nM. Phase 1.

S8280New

IMR-1

IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μmol/L.

S2711

YO-01027 (Dibenzazepine)

YO-01027 (Dibenzazepine) 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.

S2714

LY411575

LY411575 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.

S8018

PF-03084014 (PF-3084014)

PF-03084014 (PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2.

S7673

L-685,458

L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.

S7399

FLI-06

FLI-06 is a novel inhibitor of Notch signaling with EC50 of 2.3 μM.

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

RO4929097

RO4929097 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.

S2660

MK-0752

MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.

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.

S7169New

LY3039478

LY3039478 is a novel and orally bioavailable inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with IC50 of ~1 nM. Phase 1.

S8280New

IMR-1

IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μmol/L.

S2711

YO-01027 (Dibenzazepine)

YO-01027 (Dibenzazepine) 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.

S2714

LY411575

LY411575 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.

S8018

PF-03084014 (PF-3084014)

PF-03084014 (PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2.

S7673

L-685,458

L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.

S7399

FLI-06

FLI-06 is a novel inhibitor of Notch signaling with EC50 of 2.3 μM.

Tags: Gamma-secretase inhibition | Gamma-secretase inhibitor Notch | Gamma-secretase activity | Gamma-secretase assay | Gamma-secretase cleavage | Gamma-secretase inhibitor in clinical trial | Gamma-secretase inhibitor review