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gamma-secretase inhibitor XXI
- Development stage
- Unknown
- Lead developer
- Merck
- Modality
- Small Molecules
- Administration
- Parenteral
01
Overview
GSI-XXI, also known as Compound E, is a potent, cell-permeable, and selective non-transition state inhibitor of the γ-secretase enzyme complex. It is widely utilized as a research tool to investigate the Notch signaling pathway, as γ-secretase is the protease responsible for the intramembrane cleavage of the Notch receptor, which releases the Notch intracellular domain (NICD) to initiate gene transcription. In preclinical oncology research, GSI-XXI is used to evaluate the role of Notch signaling in cancer stem cell maintenance, tumor progression, and chemoresistance. Unlike some other gamma-secretase inhibitors (such as GSI-I), GSI-XXI is highly specific for γ-secretase and does not typically exhibit off-target proteasome inhibition, making it a valuable control for distinguishing Notch-dependent biological effects.
- Other names
- (S,S)-2-[2-(3,5-difluorophenyl)acetylamino]-N-(5-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)propionamide
02
Targets
GSEC (Gamma-Secretase Complex)
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