YK-4-250 Mitigates Gastrointestinal Radiation Syndrome and Promotes Overall Survival Following Partial Body Radiation Injury

Authors

• Vidya P. Kumar, Uniformed Services University of the Health Sciences
• Yali Kong, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Kan Wang, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Asa R. Britton-Jenkins, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Stanton Dulan, Oakwood University
• Landon L. Moore, The University of Oklahoma Health Sciences Center
• Debra Saunders, The University of Oklahoma Health Sciences Center
• Randal May, The University of Oklahoma Health Sciences Center
• Rheal Towner, The University of Oklahoma Health Sciences Center
• Sanchita P. Ghosh, Uniformed Services University of the Health Sciences
• Courtney W. Houchen, The University of Oklahoma Health Sciences Center
• Milton L. Brown, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow

ORCID

0009-0008-7575-2043 (Kong), 0009-0003-2290-4617 (Britton-Jenkins), 0009-0009-0489-8245 (Brown)

Document Type

Article

Publication Date

2026

DOI

10.1038/s41598-026-53734-7

Publication Title

Scientific Reports

Volume

Advance online publication

Pages

27 pp.

Abstract

Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4-250, a Tempol-conjugated angiotensin receptor blocker (TCARB). YK-4-250 selectively inhibits the AT1R and exhibits antioxidant properties like Tempol and has a no observed adverse effect level (NOAEL) greater than 100 mg/kg. A single daily oral dose of 20 mg/kg of YK-4-250, administered either prior to or after 50% lethal dose (LD₅₀) of partial body irradiation (PBI), improved overall survival significantly (by 25-30% above vehicle group) and enhanced GI function by day 7. Additionally, YK-4-250's paramagnetic properties enable MRI monitoring, allowing visualization of drug delivery to target tissues. These findings suggest that YK-4-250 is a promising candidate for protecting and mitigating radiation-induced injury resulting in improved outcomes in GI-ARS.

Rights

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Original Publication Citation

Kumar, V. P., Kong, Y., Wang, K., Britton-Jenkins, A. R., Dulan, S., Moore, L. L., Saunders, D., May, R., Towner, R., Ghosh, S. P., Houchen, C. W., & Brown, M. L. (2026). YK-4-250 mitigates gastrointestinal radiation syndrome and promotes overall survival following partial body radiation injury. Scientific Reports. Advance online publication. https://doi.org/10.1038/s41598-026-53734-7

Repository Citation

Kumar, V. P., Kong, Y., Wang, K., Britton-Jenkins, A. R., Dulan, S., Moore, L. L., Saunders, D., May, R., Towner, R., Ghosh, S. P., Houchen, C. W., & Brown, M. L. (2026). YK-4-250 mitigates gastrointestinal radiation syndrome and promotes overall survival following partial body radiation injury. Scientific Reports. Advance online publication. https://doi.org/10.1038/s41598-026-53734-7