Sigma-2 receptor ligand drug conjugates as antitumor compounds, methods of synthesis and uses thereof
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. At least one described molecular species exhibits an IC.sub.50 value below 5 .mu.M against human pancreatic cancer cells in vitro. Administration of this species promoted shrinkage of pancreatic cancer tumors in a murine model system in vivo, and led to 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.
Hawkins; William (St. Louis, MO), Mach; Robert (St. Louis, MO), Spitzer; Dirk (St. Louis, MO), Vangveravong; Suwanna (St. Louis, MO), Van Tine; Brian (St. Louis, MO)
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