M01

M01 is a small molecule identified as a claudin-5 interaction inhibitor. It functions as a drug enhancer by transiently permeabilizing the blood-brain barrier (BBB). This permeabilization occurs because M01 preferentially binds to the extracellular domain of claudin-5, which weakens trans-interactions between adhering cells. This action leads to a decrease in membranous claudin-5 levels through internalization and transcriptional downregulation, thereby enabling the paracellular passage of small molecules. This mechanism facilitates the entry of neuropharmaceuticals into the brain and has been shown to improve the delivery of cytostatic drugs, such as paclitaxel, to the brain, consequently reducing orthotopic glioblastoma growth.