In vitro interaction of a novel neutrophil growth factor with human liver microsomal cytochromes P450 and the contribution of UDP-glucuronosyltransferases to its metabolism

0368606 - ÚEB 2012 RIV GB eng J - Článek v odborném periodiku
Siller, M. - Anzenbacher, P. - Anzenbacherová, E. - Doležal, Karel - Strnad, Miroslav
In vitro interaction of a novel neutrophil growth factor with human liver microsomal cytochromes P450 and the contribution of UDP-glucuronosyltransferases to its metabolism.
Xenobiotica. Roč. 41, č. 11 (2011), s. 934-944. ISSN 0049-8254. E-ISSN 1366-5928
Grant CEP: GA ČR GA301/08/1649
Výzkumný záměr: CEZ:AV0Z50380511
Klíčová slova: DRUG-DRUG INTERACTIONS * SUBSTRATE-SPECIFICITY * R-ROSCOVITINE * GLUCURONIDATION * CELLS
Kód oboru RIV: EF - Botanika
Impakt faktor: 1.791, rok: 2011

1. Neutrophil growth factors (NGFs) stimulate neutrophil growth and survival. The first synthetic cytokinin-derived NGF was recently discovered and is a prospective drug owing to its potential use in anti-inflammatory therapy. The metabolism of some cytokinin-derived drugs (e.g. R-roscovitine, olomoucine II) has already been studied and it has been shown that they may give rise to drug-drug interactions. 2. In this in vitro study, the interactions of the novel neutrophil growth factor NGF1568 with two of the main classes of human drug-metabolizing enzymes, cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs), were tested. Of the CYPs evaluated, NGF1568 was found to inhibit only CYP2C9, by an uncompetitive mechanism and with a K(i) value of 349 mu M.
Trvalý link: http://hdl.handle.net/11104/0202903