LY411575

LY411575 is a cell-permeable γ-secretase inhibitor (IC₅₀ = 0.14 nM) that blocks Notch activation in vitro at 500 µM (Curry et al.; Czirr et al.) via γ-Secretase inhibition. Notch is a transmembrane receptor that plays a key role in cell fate decisions including cell proliferation, differentiation, and apoptosis.

DIFFERENTIATION

• Promotes neuronal differentiation of neural progenitor cells derived from mouse embryonic stem (ES) cells (Abranches et al.; Aranha et al.).
• Promotes goblet cell differentiation in mouse intestine and cultured colonic organoids (Okamoto et al.; Yui et al.).
• Induces hair cell differentiation from inner ear stem cells in vitro, and transdifferentiation of supporting cells into hair cells in vivo (Bramhall et al.; Mizutari et al.).
• Causes premature differentiation of Her4-positive progenitors into neurons in zebrafish (Dirian et al.).

CANCER RESEARCH

• Induces apoptosis in primary and immortalized Karposi's sarcoma cells (Curry et al.).