Background:

FLI-06 is a novel inhibitor of Notch signaling with EC50 value of 2.3uM [1].
Notch signaling plays an important role in numerous cell-fate decisions, and its aberrant activity leads to cancer and developmental disorders [1].
Treatment of HeLa NotchΔE-eGFP cells with FLI-06 resulted in accumulation of NotchΔE-eGFP and reduced NICD-eGFP production. The phenotype was fully reversible within 1–4 h when washing out of FLI-06, which indicated that FLI-06 is not acutely toxic in cells [1]. In FLI-06 treated cells, Aβ secretion reduced significantly but not APPCTF accumulation, suggesting that FLI-06 acts upstream of α-secretase and β-secretase cleavage. Immunofluorescence analysis of HeLa cells revealed that FLI-06 caused a complete disruption of the Golgi, which can be caused by interfering with membrane trafficking in the early secretory pathway or by disassembly of the microtubules17. FLI-06 inhibited ER exit and also elicited the tubule-to-sheet phenotype, which are related to each other [1].
参考文献:
[1]. Krämer A, Mentrup T, Kleizen B, et al. Small molecules intercept Notch signaling and the early secretory pathway. Nat Chem Biol, 2013, 9(11): 731-738.