Development of YK-4-250, a radiation mitigator of GI-ARS
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AI187033
- Recipient
-
Old Dominion University UEI ELA9KB9GJCN8 Part of Old Dominion University Research Foundation
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,101,718
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 31% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- Virginia, USA
Award details come from USAspending.gov.
Description
- Abstract
- Gastrointestinal (GI) toxicity remains a significant contributor to mortality following exposure to ionizing radiation (IR), leading to GI acute radiation syndrome (GI-ARS). Current lack of effective therapy for GI-ARS underscores the critical need for medical countermeasures (MCM). This study aims to investigate the mechanisms regulating the renin-angiotensin system (RAS) and reactive oxygen species (ROS) signalling through the AT1 receptor to mitigate GI-ARS. The research introduces a novel, selective and potent tempol-ARB conjugate, YK-4-250, targeted to the AT1 receptor. Preliminary data show that oral administration of 20 MG/KG YK-4-250 at 24, 48 and 72 hours after exposure to 14.3 GY partial body irradiation (PBI) significantly mitigated GI-ARS in mice, leading to GI-recovery by day 7 and an 88% overall 30-day survival. The hypothesis postulates that IR activates RAS, elevating ANG II levels, causing oxidative damage and triggering pro-inflammatory cytokine release, ultimately contributing to acute GI-ARS. YK-4-250 is proposed as an effective radiation mitigator, with specific aims including assessing improved safety vehicle formulations, measuring basic in vivo safety, defining pharmacokinetics, determining pharmacodynamics, and evaluating survival efficacy in GI-ARS and pulmonary fibrosis models. Our final aim explores the concept that AT1R knockout mimics YK-4-250 in mitigating GI injury and prolonging post-radiation survival. The study seeks to perform formulation development for YK-4-250 for use in vivo studies, identify molecular mechanisms enhancing cytoprotective function, and investigate its utility in mitigating IR-induced lung fibrosis. Successful completion of these studies is anticipated to advance YK-4-250's development as a effective radiation mitigator for GI-ARS, potentially expanding its application as a broader medical countermeasure.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $548,931 | |
| Original award | $552,787 |
Quick answers
Who received award U01AI187033?
U01AI187033 was awarded to Old Dominion University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on April 25, 2025.
How much is award U01AI187033 worth?
$1,101,718 has been obligated on U01AI187033.
Which agency awarded U01AI187033?
National Institute of Allergy and Infectious Diseases (National Institutes of Health) awarded U01AI187033, with funding from Office of the Director (National Institutes of Health).
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award