 This study aimed to identify active DNA enzymes that can cleave VEGFR, 1M-IN-A, and investigate their anti-angiogenic activity in various model systems. DT-18 was selected as a lead molecule and demonstrated significant anti-angiogenic activity in rat corneal vascularization, mouse melanoma, and human NPC xenograft models. DCMI showed a reduction of CTRANS parameter, reflecting tumor microvascular permeability in the treated mice. Intravenous administration of DT-18 to healthy mice caused no substantial toxicities, suggesting its potential as a therapeutic agent for cancer treatment. This article was authored by Liang Function, Qin Zhu, Ying Wang, and others.