ZR2002

ZR2002 is a first-in-class dual-acting "combi-molecule" designed to simultaneously inhibit the epidermal growth factor receptor (EGFR), including its aggressive mutant form EGFRvIII, and induce DNA damage. Developed by researchers at the Research Institute of the McGill University Health Centre (RI-MUHC), it was specifically engineered to treat glioblastoma multiforme (GBM), a malignancy where EGFRvIII expression often correlates with resistance to standard chemotherapy and apoptosis. ZR2002 is designed to cross the blood-brain barrier; however, preclinical studies indicate that its efficacy is limited by metabolic oxidation, which degrades its DNA-damaging function in vivo. This metabolic instability led to the development of second-generation analogs like AF143. In intracranial mouse models of glioblastoma, ZR2002 has demonstrated the ability to delay tumor growth and significantly prolong overall survival.