Recent advances in bioreductive drug targeting |
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Authors: | Naylor M A Thomson P |
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Affiliation: | Gray Laboratory Cancer Research Trust, P.O. Box 100, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, United Kingdom. naylor@graylab.ac.uk |
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Abstract: | Advances in the chemistry of bioreductive drug activation have led to the design of hypoxia-selective drug delivery systems. These prodrugs, comprising a bioreductive "trigger", "linker" and "effector" were first explored with nitrobenzyl quaternary ammonium mustards. Alternative nitroheterocycles were subsequently developed, together with new avenues of prodrug activation in ADEPT and GDEPT. Major advances have also been made in utilising indolequinone reductive chemistry based upon an appreciation of the kinetics of oxygen-sensitive reductive elimination. |
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