Uses
CYP3cide is a potent and selective time dependent inactivator of Cytochrome P450 3A4 (CYP3A4). CYP3A4 is an important enzymes involved in the metabolism of xenobiotics in the human body and constitutes to about a quarter of all CYPs in the human body. CYP3cide provides a useful in vitro tool in defining the individual roles of CYP3A4 versus CYP3A5 in the metabolism of drugs.
Biological Activity
pf-4981517, also named cyp3cide, is a potent, efficient, and specific time-dependent inactivator of human cyp3a4. pf-4981517 is a very useful tool for understanding the relative roles of cyp3a4 versus cyp3a5 and the impact of cyp3a5 genetic polymorphism on a compound's pharmacokinetics. pf-4981517 is a lipophilic compound with a pka which will render it cationic at physiological ph. thus, it is possible that if incubate with high concentrations of microsomes, it can nonspecifically partition into microsomal phospholipid, and its apparent potency will be reduced. pf-4981517 should be useful to investigators seeking to delineate the relative contribution of cyp3a4 versus cyp3a5 in the metabolism of compounds cleared by cyp3a.robert l. walsky, r. scott obach, ruth hyland, ping kang, sue zhou, michael west, kieran f. geoghegan, christopher j. helal, gregory s. walker, theunis c. goosen and michael a. zientek. selective mechanism-based inactivation of cyp3a4 by cyp3cide (pf-04981517) and its utility as an in vitro tool for delineating the relative roles of cyp3a4 versus cyp3a5 in the metabolism of drugs. dmd september 2012 vol. 40 no. 9 1686-1697.
Biochem/physiol Actions
CYP3cide is a mechanism-based inhibitor of cytochrome P4503A4 that can be used to distinguish the contributions of CYP3A4 versus CYP3A5 on drug metabolism. The IC50 values for inhibition of Midazolam 1′-Hydroxylase activity of recombinant CYP3A4 and CYP3A5 by CYP3cide are 0.3 and 17 mM, respectively.
