GNQ-9

GNQ-9 is a novel, blood-brain barrier (BBB) permeable spiroisoindolinone derivative designed as a tumor-selective therapeutic targeting NAD(P)H-quinone oxidoreductase 1 (NQO1). NQO1 is highly overexpressed in various solid tumors, including glioblastoma and pancreatic cancer, compared to normal tissues. GNQ-9 acts as a substrate for NQO1, which catalyzes its bioreduction, leading to futile redox cycling that generates high levels of reactive oxygen species (ROS). This oxidative stress induces DNA damage, endoplasmic reticulum (ER) stress, and immunogenic cell death. Additionally, GNQ-9 has been characterized as a DNA intercalator and topoisomerase II inhibitor. Preclinical studies in intracranial glioblastoma and pancreatic cancer xenograft models have demonstrated significant efficacy and a favorable safety profile, including synergy with temozolomide.

Other names

spiroisoindolinone GNQ-9