Withanolides, probes and binding targets and methods of use thereof
US8735178B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Feb 14, 2007 |
| Grant date | May 27, 2014 |
| Priority date | — |
| Expiry date | Oct 18, 2030 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC11D3/39
- WIPO fieldBasic materials chemistry
- WIPO sectorChemistry
Abstract
Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics by extracting proteins from cells that were exposed to withanolide-biotin analog. The withanolide probes can be used to monitor expression of vimentin, in tumor samples or other diseased tissues. Withaferin analogs can be used as a treatment for diverse vimentin-associated disorders, such as cancers, angiofibrotic diseases, and chronic inflammation.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.