MOPIPP is a novel indolebased chalcone that can cross the blood-brain barrier. MOPIPP inhibits the tumor progression agaisnt glioblastoma cells. MOPIPP induces cellular vacuolization as well as increases autophagosomes numbers. MOPIPP also triggers methuosis and distrupts glucose uptake and glycolytic metabolism [1] [2] [3].

MOPIPP (10 μM; 48 h) induces cellular vacuolization but does not cause cell death in U251 glioblastoma cells， exhibiting characteristics of late endosomes [1] [2]. MOPIPP (10 μM; 24 h) results an increasing LC3 fluorescence associated with the number of autophagosomes and inhibits fusion of autophagosomes with lysosomes [1]. MOPIPP (10 μM; 24 h) increases the amounts of exosomal marker proteins in vesicle fractions recovered from 293T cells [2]. MOMIPP (10 μM; 24 h and 5 h, respectively) causes early disruptions of glucose uptake and glycolytic metabolism, induces methuosis, a form of non-apoptotic cell death, in glioblastoma and other cancer cell lines [3]. MOMIPP (10 μM; 4 h and 24 h) selectively activates the JNK1/2 stress kinase pathway, resulting in phosphorylation of c-Jun, Bcl-2 and Bcl-xL [3]. Immunofluorescence [1] Cell Line: U251 glioblastoma cells Concentration: 10 μM Incubation Time: 24 hours; incubated with 2.5 μg/ml Acridine Orange for 45 min Result: Caused accumulation of autophagosome markers. Increased punctate LC3 fluorescence and suggested an increase in the number of autophagosomes in cells. Western Blot Analysis [3] Cell Line: U251 glioblastoma cells Concentration: 10 μM Incubation Time: 4 and 24 hours Result: Triggered increaseing phosphorylation of Bcl-2 and Bcl-xL, accompanied the activation of JNK.

MOMIPP (80 mg/kg; i.p.; single dose) readily penetrates the bloodbrain barrier in female Swiss Webster Mice and (80 mg/kg; i.p.; every 24 h; 15 d) is effective in suppressing progression of intracerebral glioblastoma xenografts in female NCR-Foxn1 mice [3]. Animal Model: Intracerebral xenograft model in NCR-Foxn1 mice (female, 7-8 weeks, injected with U251- LUC cells) [3] Dosage: 80 mg/kg Administration: Intraperitoneal injection; every 24 hours for 15 days; monitored tumor progression by BLI on the days 7, 11, 15 Result: Significantly inhibited tumor progression.