ZRS1

**ZRS1** is an experimental, preclinical type I EGFR-DNA combi-molecule developed in an academic cancer-drug research program. It is a stabilized methyltriazene prodrug and second-generation derivative of RB107, designed to enter tumors and degrade to the quinazoline EGFR inhibitor FD105 and a DNA-methylating methyldiazonium species through the intermediate BJ2000. ZRS1 also generates acetylated FD105, termed FD105Ac, in vivo; FD105Ac was reported as a major and more potent EGFR-inhibitory metabolite. In tumor models, ZRS1 inhibited EGFR signaling, caused DNA damage, activated p53-associated responses, and suppressed tumor growth. Its antitumor activity is influenced by O6-methylguanine-DNA methyltransferase expression, which can repair DNA lesions produced by methylating agents.