Sigma-2 receptor ligand drug conjugates as antitumor compounds, methods of synthesis and uses thereof
US10975069B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | May 30, 2019 |
| Grant date | Apr 13, 2021 |
| Priority date | — |
| Expiry date | May 30, 2039 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D471/08
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.