ACXT-3102 (SW V-49) is a cancer-specific drug conjugate and ferroptosis inducer consisting of a pro-apoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT/SLC7A11 (des-methyl Erastin, dm-Erastin), exhibits potent, targeted therapeutic for pancreatic cancer cells.
SW V-49 overcomes the chemotherapeutic plateau of dm-Erastin via enhanced drug uptake
shows potent cytotoxic response effect against PANC-1 cells with IC50 of 4.1 uM, 17-fold more effective than an equimolar mix of SV119 and dm-Erastin.
SW V-49 inhibits cell viability of multiple human pancreatic cancer organoid cultures with IC50 of 1.84 uM.
SW V-49 reduces tumor growth and improves survival in syngeneic and patient-derived xenograft models of pancreatic cancer.
SW V-49 competes for the sigma-2 receptor with known sigma-2 binders and activates cargo-specific signaling pathways.