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, at a concentration of 10 μM, has been observed to induce cellular changes in various cancer cell lines without causing cell death. Specifically, in U251 glioblastoma cells over a 48-hour incubation period, MOPIPP leads to cellular vacuolization reflective of late endosomes, whereas a 24-hour treatment enhances LC3 fluorescence and autophagosome numbers but prevents their fusion with lysosomes. Additionally, this treatment increases exosomal marker protein levels in vesicle fractions from 293T cells. Conversely, MOMIPP disrupts glucose uptake and glycolytic pathways at the same concentration and time frames, driving methuosis in glioblastoma and other cancer types. It also selectively activates JNK1/2 stress kinase pathway features, notably phosphorylating c-Jun, Bcl-2, and Bcl-xL. Immunofluorescence and Western Blot Analyses further detail MOPIPP's and MOMIPP’s impacts on U251 cells, from autophagosome marker accumulation and LC3 fluorescent puncta increase to the phosphorylation of Bcl-2 and Bcl-xL, illustrating the activation of JNK and potentially delineating a mechanism for its effects on cancer cell biology.

MOMIPP, administered at 80 mg/kg via intraperitoneal injection, effectively crosses the blood-brain barrier in female Swiss Webster mice and, when given once every 24 hours for 15 days, significantly reduces the growth of intracerebral glioblastoma xenografts in female NCR-Foxn1 mice. In the specified animal model, female NCR-Foxn1 mice, 7-8 weeks old and injected with U251-LUC cells, were observed. The consistent dosage and administration led to a notable inhibition of tumor progression, as monitored by Bioluminescence Imaging (BLI) on days 7, 11, and 15, demonstrating the compound's efficacy in suppressing tumor growth.