FPDT (2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole) is an anti-glioblastoma agent. FPDT displays cytotoxic with IC₅₀ values of 44-68 μM for GBM cells and >100 μM for human astrocytes HA. Besides, Anti-glioblastoma activity of FPDT is linked to downregulation of the AKT pathway. FPDT (0-100 µM; 48 h) shows anti-proliferative activity with IC₅₀ values of 53.53, 44.98, 55.20, 56.37, 67.73, >100 μM for T98G, U87MG, LN229, LUB04, LUB07 cells and human astrocytes HA, respectively. Besides, FPDT  enhances an inhibitory effect of TMZ on the viability of GBM cell. Furthermore, This compound inhibits cell viability by decreasing DNA synthesis. Besides, Treatment with the highest 100 μM concentration of FPDT reduces DNA synthesis to 13, 13, 18, 9, or 14% respectively in T98G, U87MG, LN229, LUB04, or LUB07 cells as compared to the DMSO-treated cells. What’s more, FPDT (0-100 μM; 48 h) decreases the colony number of T98G, U87MG, LN229, LUB04, and LUB07 cells in a dose-dependent manner. Moreover, FPDT (25 μM; 24 h) inhibits the ability of T98G, U87MG, and LN229 cells to migrate and significantly lower the number of cells.

FPDT shows that anti-glioblastoma activity is linked to the downregulation of the AKT pathway.

FPDT inhibited phosphorylation of MEK, ERK, RSK90 kinases as well as CREB protein in non-small lung carcinoma cells. Besides, FPDT leads to the downregulation of p-GSK3β and p-AKT in T98G cells. While, The level of total AKT and GSK3β remained unchanged. Moreover, The results imply that FPDT decreases phosphorylation, but not the expression of AKT and GSK3β. Besides, Pretreatment with PDGF-BB, an AKT activator, partially protected cells from death caused by FPDT. In summary, FPDT is an anti-glioblastoma agent. Besides, FPDT shows anti-proliferative activity for GBM cells and astrocytes. Moreover, FPDT inhibits proliferation and the ability to migrate for GBM cells. Furthermore, FPDT decreases the phosphorylation level of GSK3β and AKT.