grant
Development of YK-4-250, a radiation mitigator of GI-ARS
Organization OLD DOMINION UNIVERSITYLocation NORFOLK, UNITED STATESPosted 25 Apr 2025Deadline 31 Mar 2030
NIHUS FederalResearch GrantFY2025ACE2Active OxygenAcuteAcute Radiation SyndromeAdvanced DevelopmentAdverse Late EffectsAdverse effectsAlimentary CanalAngIIAngiotensin AT1 ReceptorAngiotensin IIAngiotensin II Type 1 ReceptorAngiotensin ReceptorAntioxidantsAtomic WarfareBioavailabilityBiological AvailabilityBlood PlasmaBody TissuesBreathing MechanicsCAT scanCT X RayCT XrayCT imagingCT scanCell BodyCell Communication and SignalingCell ProtectionCell SignalingCellsCessation of lifeComputed TomographyCutaneousCytoprotectionDNADataDeathDeoxyribonucleic AcidDevelopmentDigestive TractDoseDrug KineticsDrugsErythrocupreinExcretory functionExposure toFibrosisFormulationGI Stem cellGI TractGastrointestinal InjuryGastrointestinal TractGastrointestinal tract structureGene ExpressionGenerationsHealthHemocupreinHistologicHistologicallyHistologyHourImageImpairmentInflammationInflammatoryIntermediary MetabolismIntestinalIntestinesIntracellular Communication and SignalingInvadedIonizing Electromagnetic RadiationIonizing radiationKO miceKnock-outKnock-out MiceKnockoutKnockout MiceLD-50LD50Late EffectsLethal Dose 50LipidsLungLung Respiratory SystemLung Tissue FibrosisMOF syndromeMR ImagingMR TomographyMRIMRIsMagnetic Resonance ImagingMeasuresMedical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceMedicationMetabolic ProcessesMetabolismMiceMice MammalsModelingMolecularMonitorMucosaMucosal TissueMucous MembraneMultiple Organ Dysfunction SyndromeMultiple Organ FailureMurineMusNADPH OxidaseNMR ImagingNMR TomographyNatural DisastersNuclear AccidentsNuclear Magnetic Resonance ImagingNuclear WarfareNull MouseOralOral AdministrationOral Drug AdministrationOrganOutcomeOxidative StressOxygen RadicalsPharmaceutical PreparationsPharmacodynamicsPharmacokineticsPhenocopyPhysiologicPhysiologic AvailabilityPhysiologicalPlasmaPlasma SerumPlayPro-OxidantsProductionProfibrotic factorProfibrotic signalPropertyProteinsPulmonary FibrosisRadiationRadiation DoseRadiation Dose UnitRadiation ToxicityRadiation exposureRadiation induced damageRadiation-Ionizing TotalRadiotoxicityReactive Oxygen SpeciesReceptor ProteinReceptor, Angiotensin, Type 1RecoveryRenin-Angiotensin SystemResearchResolutionRespiratory MechanicsReticuloendothelial System, Serum, PlasmaRoleSafetySignal TransductionSignal Transduction SystemsSignalingSolidSpecific qualifier valueSpecifiedSuperoxide DismutaseTestingTimeTissuesTomodensitometryToxic effectToxicitiesX-Ray CAT ScanX-Ray Computed TomographyX-Ray Computerized TomographyXray CAT scanXray Computed TomographyXray computerized tomographyZeugmatographyabsorptionalimentary tractangiotensin II type I receptorangiotensin converting enzyme 2angiotensin converting enzyme IIappropriate dosebehavior observationbehavioral observationbiological signal transductionbowelcatscancomputed axial tomographycomputer tomographycomputerized axial tomographycomputerized tomographycytocupreincytokinecytoprotectivedetermine efficacydevelopmentaldigestive canaldrug/agenteffective therapyeffective treatmentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationefficacy studyevaluate efficacyexamine efficacyexcretionfibrosis in the lunggastrointestinalgastrointestinal stem cellgut progenitorgut stem cellimagingimprovedin vivoinjury to tissueintestinal cryptintestinal progenitorintestinal stem cellsintraoral drug deliveryionizing outputirradiationknock-out animalknockout animallung fibrosismanufacturemedical countermeasuremembermortalitymultiorgan failuremultiple organ system failurenano-molarnanomolarnon-contrast CTnoncontrast CTnoncontrast computed tomographynovelnuclear attacknuclear disasternuclear eventnuclear incidentoptimal drug dosageoptimal drug doseoxidative damageoxidative injurypreventpreventingradiation damageradiation mitigatorradiation poisoningradiological mitigatorradiomitigatorreceptorresolutionssafety assessmentscreeningscreeningssocial rolesubcutaneoussubdermaltargeted agenttempoltissue injury
Description preview
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…
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