ZQJ29

ZQJ29 is a **novel cyano-substituted dimer derivative of artemisinin**, rationally designed to target **poly(ADP-ribose) polymerase 1 (PARP1)** in pancreatic cancer. It is the first reported artemisinin derivative to act as a potent PARP1 inhibitor. ZQJ29 exhibits pronounced **anti-pancreatic cancer activity** both in vitro and in animal models and demonstrates strong selectivity, showing nanomolar-range cytotoxicity against pancreatic cancer cell lines while being less toxic to normal cell lines. Its mechanism involves **PARP1 inhibition**, leading to increased expression of TP53, inhibition of the SLC7A11/GPX4 pathway, and subsequent induction of **ferroptosis** (a form of regulated cell death characterized by iron-dependent lipid peroxidation) in pancreatic cancer cells. ZQJ29 also shows superior safety and antitumor efficacy compared to oxaliplatin and is a foundational candidate for further preclinical antineoplastic drug development targeting ferroptosis in pancreatic cancer[1][3][4][5][7][9][11].