Figure 2.

Biochemical modulators of tumor BBB permeability. To selectively open the BBB in the tumor volume, the following biochemical modulators have been applied: ATP-sensitive potassium channel (K_ATP channel) activator minoxidil sulfate (MS), calcium-activated potassium channel (K_Ca channel) activator NS1619, phosphodiesterase 5 (PDE5) inhibitor vardenafil (Levitra), bradykinin type 2 receptor (B2R) activator bradykinin (BK) or BK analogs such as RMP-7, adenosine 2A receptor (A2AR) agonist Lexiscan, papaverine, and microRNAs such as miR-B2-3P. These effects can be blocked in the presence of several inhibitors, such as glibenclamide for K_ATP channel, iberiotoxin for K_Ca channel, HOE or iberiotoxin for B2R, SCH58261 for A2AR. The depicted signaling cascades have been suggested to be involved in the regulation of permeability.