γ-secretase Inhibitor

ELND 006 (Compound 30) is a metabolically stable γ-secretase inhibitor designed to selectively inhibit amyloid beta (Aβ) generation while sparing Notch signaling. It was developed through a synthetic strategy emphasizing diversity and chirality. ELND 006, along with its analog ELND007 (Compound 34), progressed into human clinical trials. In preclinical studies, both compounds demonstrated effective reduction of Aβ levels in vitro and in vivo. Comparisons with other γ-secretase inhibitors like Semagacestat, Begacestat, and Avagacestat underscored their potency and specificity in lowering Aβ levels in cerebrospinal fluid (CSF) of healthy human volunteers, suggesting potential therapeutic efficacy in Alzheimer's disease.

L-Citronellol ((S)-3,7-Dimethyloct-6-en-1-ol) is a natural product with anti-allergic and neuroprotective effects. L-Citronellol inhibits mast cell activation and the release of inflammatory factors by inhibiting the ERK pathway. L-Citronellol inhibits BACE1/PSEN1 and AChE, reduces TNF-α expression and lipid peroxidation, demonstrating the potential of multi-target anti-Alzheimer's disease (AD).

LY900009 is a potent and orally active, First-in-class inhibitor of Notch signaling via selective inhibition of the γ-secretase protein (GSI). LY900009 inhibits Notch signalling in tumor cell lines and endothelial cells (IC₅₀=0.005-20 nM). LY900009 can be used for advanced cancer research.

Amyloid-β-IN-2 (Compound EX.112) is a selective γ-secretase inhibitor. Amyloid-β-IN-2 inhibits Aβ42 secretion in H4 cells with an EC₅₀ value of 226 nM. Amyloid-β-IN-2 is promising for research of Alzheimer's disease (AD) and other diseases related to Aβ deposition.

Amyloid-β-IN-3 (EX.113) is a selective γ-secretase inhibitor. Amyloid-β-IN-3 inhibits Aβ42 secretion in H4 cells with an EC₅₀ value of 148 nM. Amyloid-β-IN-3 regulates the γ-secretase catalytic activity to decrease Aβ42 production, thereby alleviating neurotoxicity caused by Aβ deposition. Amyloid-β-IN-3 is promising for research of Alzheimer's disease (AD).

Theasaponin E1 is an orally effective tea saponin. Theasaponin E1 inhibits the proliferation of cancer cells by activating apoptosis. Theasaponin E1 inhibits angiogenesis in ovarian cancer cells and HUVECs by reducing the expression of VEGF. Theasaponin E1 upregulates the phosphorylation level of ATM protein and the expression level of PTEN protein in cancer cells, decreases the phosphorylation levels of Akt, mTOR, p70S6K and 4E-BP1 proteins, downregulates the expression of HIF-1α and NF-κB, and reduces the protein expression of Notch ligands Dll4 and Jagged1. Theasaponin E1 exerts neuroprotective effects by inhibiting the activity of acetylcholinesterase, activating α-secretase and neprilysin, reducing the concentration of Aβ, and inhibiting the activities of β-secretase and γ-secretase. Theasaponin E1 exhibits toxic effects on cancer cells and quinone reductase-inducing activity, and inhibits tumor growth in vivo. Theasaponin E1 induces ferroptosis in Pomacea canaliculata by synergistically disrupting cholesterol homeostasis and sphingolipid metabolism. Theasaponin E1 possesses anti-biofilm activity against Candida albicans. Theasaponin E1 can be used in the research of ovarian cancer, obesity, Alzheimer's disease and fungal infections.

Z-Ile-Leu-aldehyde (Z-IL-CHO) is a potent and competitive peptide aldehyde inhibitor of γ-secretase and notch.

Z-LLNle-CHO (Z-Leu-Leu-Nle-CHO) is a γ-secretase inhibitor I. Z-LLNle-CHO induces caspase and ROS-dependent apoptosis by blocking the Akt-mediated pro-survival pathway. Z-LLNle-CHO can be used in cancer research, such as breast cancer and leukaemia.

ELN318463 is an amyloid precursor protein (APP) selective γ-secretase inhibitor. ELN318463 shows differential inhibition of presenilin (PS1)- and PS2-comprised γ-secretase with EC₅₀s of 12 nM and 656 nM for PS1 and PS2, respectively. ELN318463 is 51-fold more selective for PS1.

Fosciclopirox (CPX-POM) suppresses growth of urothelial cancer by targeting the γ-secretase complex. Fosciclopirox selectively delivers the active metabolite, Ciclopirox (CPX), to the entire urinary tract. Ciclopirox has anticancer activity in a number of solid and hematologic malignancies.

PSEN1-IN-2 (Compound 13K) is a PSEN1 inhibitor. PSEN1-IN-2 inhibits PSEN1-APH1A and PSEN1-APH1B complex with IC₅₀s of 6.9 and 2.4 nM. PSEN1-IN-2 can be used for Alzheimer's disease research.

(9R)-RO7185876 (Compound example 16) is a γ-secretase inhibitor. (9R)-RO7185876 inhibits Αβ42 secretion. (9R)-RO7185876 can be used for the researches of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, multi-infarct dementia, dementia pugilistica or Down syndrome.

Nirogacestat (Standard) is the analytical standard of Nirogacestat. This product is intended for research and analytical applications. 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.

L-Citronellol ((S)-3,7-Dimethyloct-6-en-1-ol) is an analytical standard for L-Citronellol (HY-W015515). This product is intended for research and analytical applications. L-Citronellol is a natural product with anti-allergic and neuroprotective effects. L-Citronellol inhibits mast cell activation and the release of inflammatory factors by inhibiting the ERK pathway. L-Citronellol inhibits BACE1/PSEN1 and AChE, reduces TNF-α expression and lipid peroxidation, demonstrating the potential of multi-target anti-Alzheimer's disease (AD).

Aβ42-IN-2 (compound example 36) is a γ-secretase modulator. Aβ42-IN-2 has an IC₅₀ of 6.5 nM for Αβ₄₂. Aβ42-IN-2 can be used for the research of Alzheimer's disease.

Demissidine is an alkaloid that can be isolated from potato. Demissidine is a promising dual inhibitors against β- and γ-secretase proteins in silico.

Aβ42-IN-1, compound 1v, is a novel, potent and orally active?γ-secretase modulator (GSM). Aβ42-IN-1 potently reduced Aβ42 levels with an IC₅₀?value of 0.091?μM without CYP3A4 inhibition. Aβ42-IN-1 shows a sustained pharmacokinetic profile.

LY3056480 is a γ-secretase inhibitor. LY3056480 inhibits the Notch signaling pathway, upregulates Atoh1, promotes hair cell regeneration, and drives supporting cell transdifferentiation. LY3056480 is applicable to research related to sensorineural hearing loss.

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.

Fosciclopirox disodium suppresses growth of urothelial cancer by targeting the γ-secretase complex. Fosciclopirox disodium selectively delivers the active metabolite, Ciclopirox (HY-B0450), to the entire urinary tract. Ciclopirox has anticancer activity in a number of solid and hematologic malignancies.