biostudies-literatureSperry MMMargarita Salas Postdoctoral grantArmy Research OfficeRP93796https://www.ebi.ac.uk/biostudies/studies/S-EPMC11421850biostudies-literatureUnknown13Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in <i>Xenopus</i>, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80eLifeIdentification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.PMC11421850UNI/551/2021W911NF-19-2-0027Kuelker AKaki SLin TVeraza RLopez RMartinez RSheehan KCharrez BWeitzel EKWood DMParry OGSesay AMIngber DEAndrijauskaite KCox-Hinshaw JPena JJSperry MMGardner EPilobello KHinshaw CJLightbown SShcherbina KDel Campo DCisneros ESleeter JJMaxwell ZPercival TJMarquez STakeda TLevin MNovak RSuper MMoore JPlaza-Oliver MYracheta JHomas ZTCano IJessop ILewandowski MIzadifar ZFotowat HBunegin LfalseIdentification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in <i>Xenopus</i>, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC802024-01-01T00:00:00Z2024 Sep2026-06-04T14:49:06.749Z2025-04-19T19:28:53.761ZS-EPMC114218503931604210.7554/eLife.93796