Background:

YO-01027, also known as dibenzazepine or DBZ, is a potent inhibitor of γ-secretase, a multisubunit aspartyl protease catalyzing the cleavage of numerous type I integral membrane proteins (such as amyloid precursor protein (APP) and Notch). YO-01027 also potently blocks amyloid precursor protein-like (APPL) and Notch cleavage, with estimated inhibition constant IC₅₀of 2.640.30 nM and 2.920.22 nM respectively, through interaction with the N-terminal fragment of Presenilin in a dose-response manner. Recent studies show that YO-01027-induced inhibition Notch signaling pathway leads to a rapid conversion of proliferative crypt cells into postmitotic cells and impairs MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells instead of postmiotic stratified cells at both preconfluent and confluent stages.

Reference

[1].Linjie Xiong, Ashley M. Woodward, and Pablo Argueso. Notch signaling modulates MUC16 biosynthesis in an vitro model of human corneal and conjunctival epithelial cell differentiation. Invest. Ophthalmol. Vis. Sci. 2011, 52(8), 5641-5646
[2].Casper Groth, W. Gregory Alvord, Octavio A. Quinones, and Mark E. Fortini. Pharmacological analysis of drosphila melanogaster γ-secretase with respect to differential proteolysis of Notch and APP. Mol. Pharmacol. 2010, 77(4), 567-574