Drug targets to overcome de novo drug-resistance in multiple myeloma
US9616051B2 · kind B2 · utility
Assignees
Inventors
Key dates
| Filing date | Jun 3, 2013 |
| Grant date | Apr 11, 2017 |
| Priority date | — |
| Expiry date | May 15, 2034 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D487/22
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Topoisomerase II alpha (topo IIα) is exported from the cell nucleus in human myeloma cells by a chromosome-maintenance protein-1 (CRM1)-dependent mechanism, resulting in topo II inhibitor resistance. The nuclear export signal (NES) of topo IIα is unique, making it a potential target for small molecule inhibitors. Small molecules NES inhibitors were identified, which inhibited binding of topo IIα to the export receptor CRM1. Inhibition was specific to topo IIα as p53 trafficking was unaffected along with topo IIα protein expression and function (decatenation). These topo IIα-specific nuclear export inhibitors may potentially lead to a new approach in circumventing drug resistance in multiple myeloma. The compounds provide a protocol for treating multiple myeloma or an oncogenic disease. Further, the topoisomerase II nuclear export signal inhibitor may be combined with a topoisomerase II inhibitor.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.