Sigma-2 receptor ligand drug conjugates as antitumor compounds, methods of synthesis and uses thereof

摘要

Methods and compositions for treating cancers such as pancreatic cancer and synovial sarcoma are disclosed. Compounds comprising a sigma-2 receptor-binding moiety and a ferroptosis-inducing moiety are described, such as the methanesulfonate salt of a compound of structural Formula IV,; , wherein n is an integer chosen from 1, 2, 3, 4, and 5, and R₂ is H or methyl. At least one described molecular species exhibits an IC₅₀ value below 5 μM against human pancreatic cancer cells in vitro. Administration of this species promoted shrinkage of pancreatic cancer tumors in a murine model system in vivo. It led to a 100% survival of experimental animals over a time course in which control therapies provided only 30% or 40% survival. Methods of synthesis of molecular species are also disclosed.