biostudies-literatureRashed FBNatural Sciences and Engineering Research Council of CanadaAlberta InnovatesTerry Fox FoundationAlberta Cancer FoundationCanadian Institutes of Health ResearchCIHR102300https://www.ebi.ac.uk/biostudies/studies/S-EPMC9038562biostudies-literatureUnknown52Solid tumours are often poorly oxygenated, which confers resistance to standard treatment modalities. Targeting hypoxic tumours requires compounds, such as nitroimidazoles (NIs), equipped with the ability to reach and become activated within diffusion limited tumour niches. NIs become selectively entrapped in hypoxic cells through bioreductive activation, and have shown promise as hypoxia directed therapeutics. However, little is known about their mechanism of action, hindering the broader clinical usage of NIs. Iodoazomycin arabinofuranoside (IAZA) and fluoroazomycin arabinofuranoside (FAZA) are clinically validated 2-NI hypoxic radiotracers with excellent tumour uptake properties. Hypoxic cancer cells have also shown preferential susceptibility to IAZA and FAZA treatment, making them ideRedox biologyCellular mechanism of action of 2-nitroimidazoles as hypoxia-selective therapeutic agents.PMC9038562MOP-36519Sokhi SRicardo CYang XHEl-Saidi HRashed FBWiebe LIKumar PNation PNIsmail IHStoica ACNarain RDiaz-Dussan DMacdonald DWeinfeld MMashayekhi FfalseCellular mechanism of action of 2-nitroimidazoles as hypoxia-selective therapeutic agents.Solid tumours are often poorly oxygenated, which confers resistance to standard treatment modalities. Targeting hypoxic tumours requires compounds, such as nitroimidazoles (NIs), equipped with the ability to reach and become activated within diffusion limited tumour niches. NIs become selectively entrapped in hypoxic cells through bioreductive activation, and have shown promise as hypoxia directed therapeutics. However, little is known about their mechanism of action, hindering the broader clinical usage of NIs. Iodoazomycin arabinofuranoside (IAZA) and fluoroazomycin arabinofuranoside (FAZA) are clinically validated 2-NI hypoxic radiotracers with excellent tumour uptake properties. Hypoxic cancer cells have also shown preferential susceptibility to IAZA and FAZA treatment, making them ide2022-01-01T00:00:00Z2022 Jun2025-04-05T11:07:21.146Z2025-04-05T11:07:21.146ZS-EPMC90385623543054710.1016/j.redox.2022.102300