To facilitate access to electronic resources for all researchers working in the field of P450 proteins and P450-containing systems, a WorldWide Web server has been established called The Directory of P450-containing Systems at < http://www.icgeb.trieste.it/p450/ >. Currently it contains the most up-to-date list of sequences of both the P450 superfamily and proteins mediating electron transfer t...

Gene therapy using the prodrug-activating enzyme P450 2B6 has shown substantial promise in preclinical and initial clinical studies with the P450 prodrugs cyclophosphamide and ifosfamide. We sought to optimize this therapy using the canine P450 enzyme 2B11, which activates cyclophosphamide and ifosfamide with Km of 80 to 160 micromol/L, approximately 10- to 20-fold lower than the Km of P450 2B6...

Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. ...

Tirapazamine (TPZ) is a bioreductive drug that exhibits greatly enhanced cytotoxicity in hypoxic tumor cells, which are frequently radiation-resistant and chemoresistant. TPZ exhibits particularly good activity when combined with alkylating agents such as cyclophosphamide (CPA). The present study examines the potential of combining TPZ with CPA in a cytochrome P450-based prodrug activation gene...

In recent years, claims of increased involvement of non-cytochrome P450 (non-P450) enzymes in the metabolism of drugs have appeared in the literature. However, no temporal summaries of the contribution of non-P450 enzymes to the metabolism of drugs have been published. Using data from human radiolabeled absorption, distribution, metabolism, and excretion studies available for a set of 125 orall...

Twenty five derivatives of the drugs terfenadine and ebastine have been designed, synthesized and evaluated as inhibitors of recombinant human CYP2J2. Compound 14, which has an imidazole substituent, is a good non-competitive inhibitor of CYP2J2 (IC(50)=400nM). It is not selective towards CYP2J2 as it also efficiently inhibits the other main vascular CYPs, such as CYP2B6, 2C8, 2C9 and 3A4; howe...

Cinnamophilin (CIN) showed protective effect against oxidative damage. Cytochrome P450-dependent monooxygenase (P450) and glutathione S-transferase (GST) are important drug-metabolizing enzymes and P450 plays an important role in drug-drug interactions. To assess the possible drug interactions, effects of CIN on mouse P450 and GST were studied. In vitro, CIN inhibited liver microsomal nifedipin...

Cytochrome P450 (P450) enzymes play a critical role in the activation and detoxication of many neurotoxic chemicals. Although research has largely focused on P450-mediatedmetabolism in the liver, emerging evidence suggests that brain P450s influence neurotoxicity by modulating local metabolite levels. As a first step toward better understanding the relative role of brain P450s in determining ne...