Research paper5-fluoro-2-pyrimidinone, a liver aldehyde oxidase-activated prodrug of 5-fluorouracil
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smProdrugs: A repository of small molecule prodrugs
2023, European Journal of Medicinal ChemistryInhibition of vertebrate aldehyde oxidase as a therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis
2020, European Journal of Medicinal ChemistryCitation Excerpt :Potential interactions of new drugs with AOX and consequences for therapeutic efficacy, half-life and availability. AOX1 can metabolically activate some prodrugs, which makes the enzyme an interesting pharmacological target for chemotherapy [51–53]. Metabolic activation of prodrugs by AOX1 has already been exploited to overcome pharmacokinetic problems and to improve bioavailability, as exemplified by the clinical development of the 5-fluoruracil precursor, 5-fluoro-2-pyrimidinone, and the 5-iodo-2-deoxyuridine precursor, 5-iodo-2-pyrimidinone-2-deoxyribose [54–58].
Aldehyde oxidase and its role as a drug metabolizing enzyme
2019, Pharmacology and TherapeuticsCitation Excerpt :Similarly, 5-FP was activated to 5-FU very efficiently by AO (KM value of 220 μM and Vmax of 8 nmol/min/mg). However, the prodrug approach failed due to lack of selectivity and or similar cytostatic activity as 5-FU (dosed by itself) (Guo et al., 1995; Porter et al., 1994). Despite these efforts, exploitation of AO for prodrug activation has not gained traction.
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