AF143

AF143 is a dual-acting 'combi-molecule' designed to simultaneously inhibit the epidermal growth factor receptor (EGFR), including its oncogenic mutant EGFRvIII, and induce DNA damage. Developed as part of a 'combi-targeting' strategy at the Research Institute of the McGill University Health Centre (RI-MUHC), AF143 is a second-generation analog of ZR2002, engineered for enhanced metabolic stability and potency. In preclinical models of glioblastoma multiforme (GBM), AF143 demonstrated the ability to cross the blood-brain barrier and significantly prolong survival in mice bearing intracranial human glioblastoma stem cell-derived tumors. Its mechanism involves blocking EGFR signaling while its DNA-targeting moiety induces cytotoxic DNA lesions, effectively addressing resistance mechanisms common in aggressive brain tumors.