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

Developing high throughput measurement of thiopurine in DNA by mass spectrometry

Award Number: R41GM136093
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/02/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2023

Group Awards By:

View Award Description

Developing high throughput measurement of thiopurine in DNA by mass spectrometry - PROJECT SUMMARY Thiopurines such as mercaptopurine are S-substituted antimetabolites used as functional analogs to natural nucleobase precursors. They are highly effective against hematologic malignancies (leukemia and lymphoma) and autoimmune diseases (inflammatory bowel diseases [IBD]), with an estimated patient population >350,000 in the US. However, the cytotoxicity of thiopurines depends on their conversion into 6-thioguanine (TG) nucleotides (TGN), which are incorporated into DNA, causing cell death by post-replicative DNA mismatch repair. They have narrow therapeutic indexes with dose-limiting hematopoietic toxicity whereas low-responders are undertreated with standard dosing. Therefore, there is enormous clinical benefit from preemptively identifying patients at risk of thiopurine toxicity and individualizing therapy to mitigate it. We propose here a high throughput method based on matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) for quantifying the pharmacological endpoint of thiopurines, TG incorporated in chromosomal DNA (DNA-TG) of white blood cells, and examine its specificity and accuracy in standard and clinical samples. To test this strategy, we propose three specific aims: Aim #1. Chemical derivatization, isolation and detection of 6-thioguanine (6-TG) by MALDI-MS. Aim #2. Examination of linear range, sensitivity, specificity and reproducibility of the method. Aim #3. Validation of high throughput 6-TG detection with biological samples. With the aim to individualize thiopurine therapy through reducing adverse reactions and obtaining optimum therapeutic efficacy for patients on thiopurine treatment, the high throughput technique facilitates continuous monitoring of thiopurine in DNA before and during the therapy. This highly translational project will likely have high impact on a large number of patients who are under chemo-treatment or thiopurine therapy for non-malignant conditions (e.g., IBD).


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: 2023 ( Subtotal = $0 )
2023	2020	TYMORA ANALYTICAL OPERATIONS LLC	1201 CUMBERLAND AVE	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	9/25/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	TYMORA ANALYTICAL OPERATIONS, LLC	1201 CUMBERLAND AVE STE 209	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	1/27/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $299,975 )
2020	2020	TYMORA ANALYTICAL OPERATIONS, LLC	1201 CUMBERLAND AVE STE 209	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	1	4/2/2020	NEW	$299,975
														Subtotal = $299,975

Grand Total All Awards = $299,975

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Developing high throughput measurement of thiopurine in DNA by mass spectrometry

Award Number: R41GM136093

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/02/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer