TABLE 1

Effect of various molybdenum hydroxylase inhibitors on the formation of metabolite M11 in monkey and human liver cytosol

These chemical inhibitor studies were carried out at 37°C in triplicate and included liver cytosol (1 mg/ml), potassium phosphate buffer (50 mM, pH 7.4), and SGX523 (5 μM) with or without the chemical inhibitors of AO and XO at the final concentrations shown. Incubations were terminated with methanol/acetonitrile after 30-min incubation. After centrifugation, the resulting supernatants were analyzed by LC/MS.

InhibitorTarget EnzymeInhibitor ConcentrationMetabolite M11 Formed
MonkeyHuman
μM% of control% of control
AllopurinolXO10091 ± 4109 ± 8
OxipurinolXO100111 ± 892 ± 2
MethotrexateXO100107 ± 888 ± 3
MenadioneAO1009 ± 0.211 ± 2
RaloxifeneAO2043 ± 616 ± 2
SKF525-AAO10095 ± 1262 ± 4