Wednesday, February 18, 2026 2/18/2026

L-Cystine Diamides as Inhibitors of L-Cystine Stone Formation in Cystinuria

Award Number: R01DK112782
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2023

Group Awards By:

View Award Description

L-Cystine Diamides as Inhibitors of L-Cystine Stone Formation in Cystinuria - Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of L-cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Current treatment of cystinuria has not changed over the last three decades. Patients are advised to drink substantial amounts of water (>4 liters/day) to reduce the concentration of free L-cystine in urine and to alkalinize the urine to increase cystine solubility, advice that challenges patient adherence. Drug therapy in severe conditions is limited to two thiol drugs that react with L-cystine to form more soluble mixed disulfides, but these drugs have poor patient compliance due to adverse reactions that, in some cases, may be life-threatening. Thus, there is a need to reduce or eliminate the risks associated with therapy for cystinuria. In this application, we propose a new approach to prevent recurrent cystine stone formation in patients with cystinuria. Our substantive in vitro studies indicate that L-cystine diamides are potent inhibitors of cystine crystallization, which is a required condition for stone formation. Our preliminary in vivo studies indicate that one compound (LH708) from this family is effective in preventing L-cystine stone formation in Slc3a1 knockout mice, which we generated in our laboratories as a model for cystinuria. Building on our in vitro and in vivo data, we will design, synthesize, and evaluate new analogs and prodrugs of L-cystine diamides with sufficient metabolic stability and oral bioavailability that can effectively inhibit L-cystine crystallization in vivo and thus prevent L-cystine stone formation. The effectiveness of these new compounds to inhibit L-cystine crystallization will be tested using a combination of in vitro fluorescence-based solubility and real-time in situ crystal growth inhibition assays. The most effective inhibitors then will be evaluated for their in vivo efficacy, safety, and bioavailability in Slc3a1 knockout mice and for their preclinical ADME-Tox properties. The combined results from these studies will enable the selection of one top drug candidate and one backup candidate for IND-directed preclinical evaluations, for which we will seek assistance from the NIH NCATS program.


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 = $0 )
2024	2021	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	10/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $522,334 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/11/2021	NON-COMPETING CONTINUATION	$522,334
														Subtotal = $522,334

Issue Date FY: 2020 ( Subtotal = $523,106 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/8/2020	NON-COMPETING CONTINUATION	$470,796
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/10/2020	NON-COMPETING CONTINUATION	$52,310
														Subtotal = $523,106

Issue Date FY: 2019 ( Subtotal = $600,172 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/8/2019	NON-COMPETING CONTINUATION	$600,172
														Subtotal = $600,172

Issue Date FY: 2018 ( Subtotal = $612,089 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/19/2018	NON-COMPETING CONTINUATION	$61,209
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/3/2018	NON-COMPETING CONTINUATION	$550,880
														Subtotal = $612,089

Issue Date FY: 2017 ( Subtotal = $621,145 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/20/2017	NEW	$621,145
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	2/22/2017	NEW	$0
														Subtotal = $621,145

Grand Total All Awards = $2,878,846

Top

All Categories

About

Search

Reports

Data Submission

Award Information

L-Cystine Diamides as Inhibitors of L-Cystine Stone Formation in Cystinuria

Award Number: R01DK112782

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer