Raltegravir is an HIV integrase inhibitor that is metabolized through glucuronidation by uridine diphosphate glucuronosyltransferase 1A1, and its use is anticipated in combination with atazanavir (a uridine diphosphate glucuronosyltransferase 1A1 inhibitor). Two pharmacokinetic studies of healthy subjects assessed the effect of multiple-dose atazanavir or ritonavir-boosted atazanavir on raltegr...

The commonmarmoset (Callithrix jacchus), a NewWorldmonkey, has potential to be an animal model for drug metabolism studies. In this study, we identified and characterized cytochrome P450 (P450) 1A1 and 1B1 in addition to the known P450 1A2 in marmosets. Marmoset P450 1A1 and 1B1 cDNA contained open reading frames encoding 512 and 543 amino acids, respectively, with high sequence identities (90%...

Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxification steps of many environmental carcinogens, the cytochromes P450 1A1, 1A2 an...

PURPOSE The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the f...

Objective(s):Cytochrome P-450 1A1 is an important enzyme in the first phase of the metabolism of some carcinogens such as polycyclic aromatic hydrocarbons (PAHs), as well as estrogen. The present study evaluates the existence of CYP1A1 polymorphism in a number of breast cancer samples. Materials and Methods: One hundred breast cancer patients and the same number of healthy controls were analyz...

When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3buten-2-one (4-OH-PBO), respectively, were formed as major metabolites. Two minor metabolites of chalcone, 4 -hydroxychalcone and 2-hydroxychalcone, were also observed. The oxidase activity affording 4-hydroxychalc...

Cytochrome P450 enzymes metabolize various endogenous and exogenous small molecular weight compounds. Transport-associated proteins, such as P-glycoprotein, multidrug resistance-associated protein and lung resistance protein are overexpressed in drug-resistant cell lines, as well as in human tumors from various histologic origins, including malignant melanoma. Little is known about the expressi...

BACKGROUND Cytochrome P450 1A, an enzyme known to metabolize polycyclic aromatic hydrocarbons (PAHs), participates in the metabolism of aristolochic acid I (AAI) in liver and kidney microsomes isolated from humans and rodents. This study was designed to investigate whether P450 1A plays a role in AAI-induced renal injury in C57BL/6 mice. METHODS Separate groups of mice were given AAI (10 mg/k...

In silico docking studies and quantitative structure-activity relationship analysis of a number of in-house cytochrome P450 inhibitors have revealed important structural characteristics that are required for a molecule to function as a good inhibitor of P450 enzymes 1A1, 1A2, 2B1, and/or 2A6. These insights were incorporated into the design of pharmacophores used for a 2D search of the Chinese ...

Key residue Val-382 in P450 1A1 has been predicted to interact with the alkoxy chain of resorufin derivatives. Therefore, we undertook a detailed analysis of substrate mobility in the active site of the P450 1A1 homology model and assessed the effect of mutations at position 382. Dynamic trajectories of 7-methoxy-, 7-ethoxy-, and 7-pentoxyresorufin indicated that 7-ethoxyresorufin would be oxid...