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.

Mohan; Royce

Bargagna-Mohan; Paola

Kim; Kyung Bo

University of Kentucky Research Foundation

Withanolides, probes and binding targets and methods of use thereof

Disclosed is a method of enhancing the response of cancer cells in a mammal to treatment with a death receptor ligand, which method comprises contacting the cancer cells with a death receptor ligand in conjunction with an effective amount of a compound described herein, for example, a cucurbitacin (I) or a withanolide (II). Also disclosed is a method of inducing apoptosis in cancer cells in a mammal, comprising contacting the cancer cells with a compound described herein, for example, a cucurbitacin (I) or a withanolide (II) and also contacting the cancer cells with a death receptor ligand, whereby apoptosis is induced in the cancer cells. ##STR00001##

Sayers; Thomas Joseph

Booth; Nancy Lynn

Henrich; Curtis J.

Brooks; Alan David

Gustafson; Kirk R.

Erickson; Karen L.

The United States of America, as represented by the Secretary, Department of Health and Human Services

Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment

withanolide

zhubný nádor

neoplasms

withanolide/zhubný nádor

Withanolides, probes and binding targets and methods of use thereof

Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment

Najkompletnejšia databáza liečivých bylín podporovaná vedou