γ secretase(notch)

LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM.

DAPT (LY-374973) is a γ-secretase inhibitor that inhibits total Aβ and Aβ42 (IC50=115 200 nM) and is orally active. DAPT is also a Notch inhibitor. DAPT induces cell differentiation, autophagy and apoptosis.

BMS-906024 (Osugacestat) is an orally available and selective inhibitor of γ-secretase, a small molecule Notch inhibitor.BMS-906024 has broad-spectrum antitumour activity against a variety of human cancer xenografts.BMS-906024 prevents the activation of all four Notch receptors, and is active against Notch1, -2, -3 and -4 receptors. BMS-906024 prevents the activation of all four Notch receptors, with IC50s of 1.6, 0.7, 3.4 and 2.9 nM for Notch1, -2, -3 and -4 receptors, respectively.

YO-01027 (DBZ) is a potent γ-secretase inhibitor.

Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most tumor cell lines tested. It effectively inhibits mutant Notch receptor activity and, in a xenograft tumor model, inhibits the expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.

Nirogacestat (PF 03084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay).

3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) is a γ-secretase inhibitor that reduces the levels of released Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).

LY900009 is a small molecule inhibitor of Notch signalling via selective inhibition of the γ-secretase protein.

Begacestat (GSI-953) is a potent and selective gamma-secretase inhibitor (γ-secretase) that inhibits Amyloid-beta production with nanomolar potency, selectively inhibits cleavage of APP in cellular level Notch cleavage assays, reverses situational memory deficits, and can be used to study Alzheimer's disease.

E2012 is a γ-secretase modulator (GSM). E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E 2012 aims at Alzheimer's disease by reduction of amyloid β-42, and induces cataract following repeated doses in the rat.

Z-Ile-Leu-aldehyde is an effective and competitive peptide aldehyde inhibitor of γ-secretase and notch.

GSI-18, a γ-secretase inhibitor, exhibits anticancer activity by mitigating anchorage-independent growth in pancreatic cancer cells through the inhibition of Notch signaling.

JLK6 was a gamma-secretase inhibitor that does not interfere with Notch signalling

JNJ-40418677 is a γ-secretase modulator that selectively blocks γ-site cleavage of the APP without affecting the processing of Notch.

γ-Secretase-IN-1 is a potent γ-secretase inhibitor that displays partial antiproliferative activity on T-47D cells and inhibits β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage.

Semagacestat (LY450139) (LY450139) is a γ-secretase blocker for Aβ42 Aβ40 Aβ38 (IC50: 10.9 12.1 12.0 nM) and also inhibits Notch signaling (IC50: 14.1 nM).

Avagacestat (BMS-708163) (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.

RO4929097 (RG-4733), a γ secretase inhibitor (IC50: 4 nM), inhibits cellular processing of Aβ40 and Notch (EC50: 14 5 nM).

L-685458 (L-685,458) is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K Akt pathway.

Cimigenoside, a constituent of Asclepias, is a γ-secretase inhibitor that inhibits the proliferation or metastasis of human breast cancer cells via the γ-secretase Notch axis.

BT-GSI, a γ-secretase inhibitor (GSI) with bone-targeting capabilities, effectively inhibits Notch signaling. Exhibiting dual action, it possesses both anti-myeloma and anti-resorptive properties, making it a promising candidate for research into multiple myeloma and related bone diseases. Additionally, BT-GSI demonstrates potential in inhibiting tumor growth and the progression of osteolytic disease.

LY3056480 is a γ-secretase inhibitor (GSI) that inhibits Notch signaling. It demonstrates potential in improving mild to moderate sensorineural hearing loss while maintaining a good safety and tolerance profile. Administered intratympanically, LY3056480 can induce hair cell regeneration and partial hearing restoration in mammals.