γ-secretase Inhibitor

DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

Compound E is a γ-secretase inhibitor. Compound E blocks β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage with IC₅₀s of 0.24, 0.37, 0.32 nM, respectively.

LY-411575 is a potent γ-secretase inhibitor with IC₅₀ of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with an IC₅₀ of 0.39 nM.

Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC₅₀ of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers.

YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC₅₀ values of 2.92 and 2.64 nM for Notch and APPL cleavage, respectively.

L505-yne is an active site-directed γ-secretase inhibitor. L505-yne blocks photoaffinity labeling of PS1-NTF, PS1-CTF, and SPP by clickable GSI photoprobes, binds the γ-secretase complex and inhibits Aβ42 production. L458-BPyne can be used for the research of Alzheimer’s disease.

EVP-0015962 is an orally active, blood-brain barrier-permeable γ-secretase inhibitor with an IC₅₀ of 3.9 μM. EVP-0015962 alters γ-secretase-mediated cleavage of amyloid precursor protein, reduces Aβ₄₂ production and increases Aβ₃₈ production. EVP-0015962 reduces Aβ aggregates, amyloid plaques and inflammatory markers in the brains of mice, and improves their cognitive impairment. EVP-0015962 can be used for the research of Alzheimer's disease.

Anti-Nicastrin Antibody (A5226A) is a monoclonal antibody against Nicastrin and an inhibitor of γ-secretase. Anti-Nicastrin Antibody (A5226A) recognizes the fully glycosylated mature presenilin enhancer in the active γ-secretase complex and inhibits its activity via competition for substrate binding. Anti-Nicastrin Antibody (A5226A) abrogates the growth of cancer cells dependent on γ-secretase activity. Anti-Nicastrin Antibody (A5226A) serves as an imaging tool to visualize the endocytic trafficking of active γ-secretase, and also acts as a detection reagent to evaluate the endocytic efficiency of γ-secretase. Anti-Nicastrin Antibody (A5226A) can be used in studies related to non-small cell lung cancer, T-cell acute lymphoblastic leukemia and Alzheimer's disease.

RO4929097 is an orally active γ secretase inhibitor with an IC₅₀ of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC₅₀ of 14 nM and 5 nM, respectively.

MK-0752 is a potent, orally active and specific γ-secretase inhibitor, showing dose-dependent reduction of Aβ40 with an IC₅₀ of 5 nM in human SH-SY5Y cells. MK-0752 crosses the blood-brain barrier. MK-0752 reduces newly generated CNS Aβ in vivo.

Crenigacestat (LY3039478) is an orally active Notch and γ-secretase inhibitor, with an IC₅₀ of 1 nM in most of the tumor cell lines tested.

L-685458 is a potent transition state analog (TSA) γ-secretase inhibitor (GSI). L-685458 inhibits amyloid β-protein precursor γ-secretase activity with IC₅₀ of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested. L685458 inhibits γ-secretase-mediated cleavage of APP-C99 and Notch-100 with IC₅₀s of 301.3 nM and 351.3 nM, respectively. L-685458 can be used for the research of alzheimer’s disease (AD) and cancers.

Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC₅₀s of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC₅₀ of 14.1 nM. Semagacestat can be used for the research of alzheimer's disease.

Nirogacestat dihydrobromide (PF-3084014 dihydrobromide) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC₅₀ of 6.2 nM. Inhibition of Notch signaling by Nirogacestat dihydrobromide while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers.

Avagacestat (BMS-708163) is a potent inhibitor of γ-secretase, with IC₅₀s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; Avagacestat (BMS-708163) also inhibits NICD (Notch IntraCellular Domain) with IC₅₀ of 0.84 nM and shows weak inhibition of CYP2C19, with IC₅₀ of 20 μM. Avagacestat can be used for Alzheimer disease research.

Itanapraced (CHF5074) is an orally active γ-secretase modulator and a non-steroidal anti-inflammatory derivative. Itanapraced reduces Aβ42 and Aβ40 secretion with IC₅₀ values of 3.6 and 18.4 μM, respectively. Itanapraced inhibits cell apoptosis of hippocampal neurons induced by oxygen and glucose deprivation (OGD). Itanapraced can be used for the research of Alzheimer's disease.

MRK-560, a chemical probe, is an orally active, brain barrier-penetrated γ-Secretase inhibitor, reducing Aβ peptide in rat brain and cerebrospinal fluid. MRK-560 decreases mutant NOTCH1 processing by selectively inhibiting PSEN1. MRK-560 can be used in studies of Alzheimer's disease and T-cell acute lymphoblastic leukaemia (T-ALL).

DAPT (GSI-IX) (GMP) is DAPT (HY-13027) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. DAPT is a potent and orally active γ-secretase inhibitor.

BMS-906024 is an orally active and selective γ-secretase (gamma secretase) inhibitor. BMS-906024 is a potent pan-Notch receptors inhibitor with IC₅₀s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity.

Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC₅₀ of 20.2 μM for γ₄₂-secretase activity.