Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2).

The protein TRAIL has a very interesting characteristic that it can preferentially cause death of cancer cells whereas normal non-transformed cells are unaffected. Thus use of TRAIL or agonist antibodies to its so-called "death receptors" has been a current focus in cancer therapy.

IC:

NCI

NIH Ref. No.:

E-050-2010

Advantages:

Cucurbitacins and withanolides can be successfully developed in combination with known TRAIL agonist have the potential of new cancer combination therapies without major toxicities.

Applications:

Use of the compounds with known TRAIL or agonist antibodies such as Mapatumumab or in combination with immunotherapeutic approaches for the treatment of cancer.

Development Status:

Pre-clinical (in vivo)

Updated On:

Apr 9, 2018

Patent Application:

61/287,139

Patent Authority:

U.S. Provisional

Patent Number:

9,238,069

Lead Inventor:

Inventor IC:

NCI

Leidos Biomedical Research, Inc.

Inventor Lab URL:

http://irp.nih.gov/pi/thomas-sayers

LPM FIrst Name:

John

LPM Last Name:

Hewes

Inv Is lead:

LPM Phone:

240-276-5515

LPM Email:

John.Hewes@nih.gov

LPM Organization:

NCI - National Cancer Institute

DTDT Classification:

Therapeutics

DTDT Description:

Therapeutics

Pat Filing Date:

2009-12-16

2012-10-26

Patent Issue Date:

2016-01-19

Publication Link:

https://www.ncbi.nlm.nih.gov/pubmed/19089423

Publication Caption:

PubMed: 19089423

Publication Title:

Nancy L. Booth et al. A cell-based high-throughput screen to identify synergistic TRAIL sensitizers.

Collaboration Sought:

Yes

Institute or Center:

Collaboration Opportunity:

Licensing only

E Number Only:

E-050-2010

Inventor First Name:

Thomas

Nancy

Alan

Inventor Last Name:

Sayers

Booth

Brooks

Use of Cucurbitacins and Withanolides for the Treatment of Cancer

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