AZ12756122

AZ12756122 is a small molecule inhibitor of Fatty Acid Synthase (FASN), an enzyme critical for de novo lipogenesis that is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC). Developed by AstraZeneca, the compound is designed to target metabolic dependencies in tumor cells, particularly those harboring EGFR mutations. By inhibiting FASN, AZ12756122 disrupts lipid metabolism, leading to the downregulation of key oncogenic signaling pathways such as EGFR/STAT3, Akt/mTOR, and MAPK. Preclinical studies indicate that it can sensitize EGFR-mutated cells to tyrosine kinase inhibitors (TKIs) like osimertinib and gefitinib, potentially overcoming resistance mechanisms associated with FASN overexpression and the maintenance of cancer stem-like cells.