PDZ1i

PDZ1i (113B7) is a inhibitor of MDA-9/Syntenin, with selective binding to the PDZ1 domain. PDZ1i inhibits radiation-induced invasion of glioblastoma (GBM) cells, radiosensitizes GBM cells, and impairs GBM-related signaling pathways (including Src/EphA2, EGFRvIII/FAK, and NF-κB). PDZ1i reduces radiation-induced secretion of invasion-related proteases (MMP-2, MMP-9, ADAM9). PDZ1i shows anti-tumor effects in nude mice bearing intracranial U1242-luc xenografts or GBM xenografts. PDZ1i can be used for the study of glioblastoma (GBM), breast cancer and prostate cancer^[1][2][3]. In Vitro:PDZ1i (50 μM, 2 h) does not further radiosensitize immortalized primary human fetal astrocytes (Im-PHFAs) but markedly enhances radiosensitivity of U87 GBM cells, and significantly decreases proliferation of U87 cells when combined with radiation^[1].
PDZ1i (50 μM, 2 h) abolishes radiation-induced invasion gains in U87 GBM cells^[1].
PDZ1i (2 h) significantly reduces phospho-EGFR (Y845) levels in both non-radiated and radiated U87-EGFRvIII GBM cells, nullifies radiation-enhanced FAK activation (phospho-FAK Y576/577), and decreases radiation-induced NF-κB activation (phospho-p65) in U87-EGFRvIII cells^[1].
PDZ1i disrupts the interaction between MDA-9/Syntenin and EGFR in both non-radiated and radiated GBM cells^[1].
PDZ1i (50 μM, 2 h) reduces radiation-induced increases in the secretion of MMP-2, MMP-9, cathepsin family members, and ADAM9 in U1242 GBM cells^[1].
PDZ1i (50 μM, 24 h) effectively crosses the human brain microvascular endothelial cell (HBMEC) barrier and inhibits the invasion of GBM6 cells, with comparable efficacy to direct pretreatment of GBM6 cells^[1].
PDZ1i (5 μM) reduces the expression levels of CD44v3 and heparan sulfate (HS) on the surface of radiation-induced extracellular vesicles (IR-tEVs) derived from breast cancer MDA-MB-231 cells, and decreases the total production of IR-tEVs^[3].
In Vivo:PDZ1i (30 mg/kg, i.p., three times per week, 2 weeks) demonstrates efficacy in reducing tumor size in nude mice bearing intracranial GBM6 xenografts^[1].
PDZ1i (30 mg/kg, i.p., 2 h before radiation, 4 consecutive days) shows enhanced anti-tumor effects when combined with radiation (2.5 Gy/day, 4 days) in nude mice bearing intracranial U1242-luc xenografts^[1].