1970
DOI: 10.1016/s0021-9258(18)63065-0
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On the Mechanism of Inactivation of Xanthine Oxidase by Allopurinol and Other Pyrazolo[3,4-d]pyrimidines

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Cited by 365 publications
(82 citation statements)
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“…The K d (dissociation constant) for oxypurinol with the human XOR is 8.6 µM [49]. The oxypurinol-XOR complex cleaves spontaneously with a short halflife of 5 h at 25 °C [50] and a half-life of only 39 minutes at 37 °C [49]. Both allopurinol and oxypurinol are purine derivatives (Figure 1.1b and c) and they were found to inhibit additional enzymes involved in the purine and pyrimidine metabolism [51].…”
Section: In Vitro Pharmacodynamics Of Allopurinolmentioning
confidence: 99%
“…The K d (dissociation constant) for oxypurinol with the human XOR is 8.6 µM [49]. The oxypurinol-XOR complex cleaves spontaneously with a short halflife of 5 h at 25 °C [50] and a half-life of only 39 minutes at 37 °C [49]. Both allopurinol and oxypurinol are purine derivatives (Figure 1.1b and c) and they were found to inhibit additional enzymes involved in the purine and pyrimidine metabolism [51].…”
Section: In Vitro Pharmacodynamics Of Allopurinolmentioning
confidence: 99%
“…43 Furthermore, allopurinol and oxypurinol bind tightly to the reduced form of xanthine oxidoreductase, but they only weakly and transiently inhibit the oxidized form; thus, these drugs may lower uric acid but not blunt the generation of superoxide anion by xanthine oxidase. 44,45 To complicate matters further, allopurinol and oxypurinol inhibit not only xanthine oxidoreductase, but also other purine-and pyrimidine-metabolizing enzymes. 46,47 In contrast, febuxostat acts selectively on xanthine oxidoreductase, 48 binds tightly to the oxidized form, and, thus, inhibits xanthine oxidase more effectively than allopurinol 49 ; yet, febuxostat increases cardiovascular risk more than allopurinol.…”
Section: Xanthine Oxidase As a Generator Of Oxidative Stressmentioning
confidence: 99%
“…The C2 of allopurinol is hydroxylated and converted to oxypurinol. In the course of the reaction, the transiently generated reduced Mo(IV) and N8 of oxypurinol form a covalent bond ( Figure 4 A) [ 33 , 34 ]. In this process, oxypurinol is thought to form a complex efficiently by rotating in the substrate-binding pocket.…”
Section: Inhibition Mechanisms Of the Inhibitorsmentioning
confidence: 99%