Compound E

• CAT Number: R065078
• CAS Number: 209986-17-4
• Molecular Formula: C₂₇H₂₄F₂N₄O₃
• Molecular Weight: 490.5
• Purity: ≥95%
• Synonyms: γ-Secretase Inhibitor XXI
• Target: Stem Cell/Wnt
• Storage: -20°C
• InChI: InChI=1S/C27H24F2N4O3/c1-16(30-23(34)14-17-12-19(28)15-20(29)13-17)26(35)32-25-27(36)33(2)22-11-7-6-10-21(22)24(31-25)18-8-4-3-5-9-18/h3-13,15-16,25H,14H2,1-2H3,(H,30,34)(H,32,35)/t16-,25+/m0/s1
• InChIKey: JNGZXGGOCLZBFB-IVCQMTBJSA-N
• SMILES: CC(C(=O)NC1C(=O)N(C2=CC=CC=C2C(=N1)C3=CC=CC=C3)C)NC(=O)CC4=CC(=CC(=C4)F)F

γ-Secretase is a multimeric aspartyl protease that regulates signaling pathways by proteolytically cleaving substrates, abrogating or releasing signaling molecules. Two well-known substrates are the carboxyl-terminal fragments (CTFs) of the receptor Notch, which has key roles in development, and that of amyloid precursor protein (APP), which is important in Alzheimer’s disease. Compound E is a potent, cell-permeable, and selective inhibitor of γ-secretase, blocking the cleavage of both APP and Notch CTFs with IC50 values of ~0.3 nM. Compound E induces neuronal differentiation, impairs ovarian folliculogenesis, and suppresses thymocyte development by preventing Notch activation by γ-secretase.

Reference

1. Biochim Biophys Acta. 2013 Dec;1828(12):2815-27. doi:
10.1016/j.bbamem.2013.04.016.

A fast growing spectrum of biological functions of γ-secretase in development and
disease.

Jurisch-Yaksi N(1), Sannerud R, Annaert W.

Author information:
(1)Laboratory for Membrane Trafficking, VIB-Center for the Biology of Disease &
Department for Human Genetics (KU Leuven), Leuven, Belgium.

γ-secretase, which assembles as a tetrameric complex, is an aspartyl protease
that proteolytically cleaves substrate proteins within their membrane-spanning
domain; a process also known as regulated intramembrane proteolysis (RIP). RIP
regulates signaling pathways by abrogating or releasing signaling molecules.
Since the discovery, already >15 years ago, of its catalytic component,
presenilin, and even much earlier with the identification of amyloid precursor
protein as its first substrate, γ-secretase has been commonly associated with
Alzheimer/’s disease. However, starting with Notch and thereafter a continuously
increasing number of novel substrates, γ-secretase is becoming linked to an
equally broader range of biological processes. This review presents an updated
overview of the current knowledge on the diverse molecular mechanisms and
signaling pathways controlled by γ-secretase, with a focus on organ development,
homeostasis and dysfunction. This article is part of a Special Issue entitled:
Intramembrane Proteases.