FLI-06

The dihydropyridine FLI-06 is a Notch pathway inhibitor with an EC50 of 2.5 mM. Signaling through Notch transmembrane receptor proteins plays an important role in cell-fate decisions; aberrant Notch activity can result in cancer and other developmental disorders. FLI-06 acts at an early stage in the secretory pathway, disrupting the Golgi and inhibiting general secretion before exit from the endoplasmic reticulum (1). Studies show that FLI-06 suppresses both the mRNA and protein expression of Notch receptor and Notch targeted genes. FLI-06 treatment of tongue cancer cells inhibits Notch signaling activation, decreasing cell proliferation, blocking cell cycle arrest, and inducing apoptosis. FLI-06 inhibited tumor growth and increased cell apoptosis in a xenograft mouse model, suggesting that FLI-06 is a potential chemotherapeutic agent for the clinical treatment of tongue tumors (2). Additional studies showed that FLI-06 inactivated Notch signaling and suppressed malignant functions in lung adenocarcinoma and esophageal squamous cell carcinoma (3,4). 1.Krämer, A. et al. (2013) Nat Chem Biol 9, 731-8. 2.Gan, R.H. et al. (2019) Onco Targets Ther 12, 7663-7674. 3.Zhang, M. et al. (2020) Cell Death Dis 11, 981. 4.Lu, Z. et al. (2018) Biomed Pharmacother 107, 1370-1376.