Invention Grant
- Patent Title: Sigma-2 receptor ligand drug conjugates as antitumor compounds, methods of synthesis and uses thereof
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Application No.: US16426791Application Date: 2019-05-30
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Publication No.: US10975069B2Publication Date: 2021-04-13
- Inventor: William Hawkins , Robert Mach , Dirk Spitzer , Suwanna Vangveravong , Brian Van Tine
- Applicant: Washington University
- Applicant Address: US MO St. Louis
- Assignee: Washington University
- Current Assignee: Washington University
- Current Assignee Address: US MO St. Louis
- Agency: Global Patent Group, LLC
- Agent Dennis Bennett; Clifford Schlecht
- Main IPC: C07D451/14
- IPC: C07D451/14 ; A61K31/517 ; A61P35/00 ; C07D471/08 ; A61K31/496 ; A61K45/06

Abstract:
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.
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