Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

TAK1 Inhibition by (5Z)-7-Oxozeaenol Analogues for Anticancer Leads

Award Number: R15CA246491
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2023

Group Awards By:

View Award Description

TAK1 Inhibition by (5Z)-7-Oxozeaenol Analogues for Anticancer Leads - Project Summary Towards the goal of developing a treatment for ovarian cancer that utilizes a new mechanism of action, we are proposing to make analogues of (5Z)-7-oxozeaenol, a resorcylic acid lactone, that inhibits TAK1. Instead of synthesizing analogues de novo, the natural product will be isolated since it is available in sufficient quantities (>500 mg per 1 L fermentation flask) and already has the requisite molecular complexity to imbue potent activity (IC50 = 8.1 nM). Preliminary data has been acquired for over 30 compounds, a suite of synthesized and isolated compounds, and their TAK1 inhibition activities have been determined. The most potent analogue was a non-aromatic difluorinated compound, the first non-aromatic resorcylic acid lactone to have a reported TAK1 inhibition. These data were recently published and a patent filed to protect these compounds for future efforts. Building off these data, we have assembled a team, led by synthetic chemistry (Croatt, PI), to use the isolated natural product (Oberlies and Pearce) as the starting material and build in the structural modifications (Runyon) that the crystal structure suggests will lead to improved activity (Burdette). These compounds will be analyzed for TAK1 inhibition, and compounds with sufficient potency will be studied for their stability and solubility properties, kinase selectivity, and activity in in vitro ovarian cancer cell lines that have increased levels of TAK1 (Burdette). The medicinal chemistry consultant (Runyon) will meet quarterly with the team to suggest modifications and areas to explore or avoid. Not only will this be significant to the study of ovarian cancer, but the students trained on this project will also benefit from the breadth of study. Illustrative of this training, the student in the Croatt lab that acquired the majority of the preliminary data for this grant obtained experience in personally running many reactions, NMRs, HPLCs, UPLCs, Mass Specs, and computational chemistry experiments. The breadth of her experience, and recent publication, placed her in a great position for her future career in academia. Similar to the experiences of this student, and within the guise of an AREA grant (R15), the PI and other members of the team have a strong history of training students.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$12,752 )
2024	2020	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Cancer Treatment Research	000	1	4/11/2024	NEW	-$12,752
														Subtotal = -$12,752

Issue Date FY: 2020 ( Subtotal = $404,939 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Cancer Treatment Research	000	1	11/26/2019	NEW	$404,939
														Subtotal = $404,939

Grand Total All Awards = $392,188

Top

All Categories

About

Search

Reports

Data Submission

Award Information

TAK1 Inhibition by (5Z)-7-Oxozeaenol Analogues for Anticancer Leads

Award Number: R15CA246491

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer