DMXAA is a xanthene which acts as a tumor vascular disrupting agent, inducing apoptosis in tumor vascular endothelium resulting in necrosis at the tumor core. It potently activates the TANK-binding kinase 1-interferon regulatory factor 3 (TBK1/IRF3) signaling pathway in leukocytes, inducing type-I-interferon (IFN) production. Specifically, DMXAA activates the mitochondria- and endoplasmic reticulum-associated protein known as stimulator of interferon genes (STING), leading to TBK1/IRF3 signaling. DMXAA signals through mouse STING but not human STING. In addition, DMXAA significantly inhibits several kinases in endothelial cells, including the vascular endothelial growth factor (VEGF) receptors VEGFR1 and VEGFR2 (IC50 = 119 and 11 μM, respectively).
