Time- and NADPH-Dependent Inhibition of P450 3A4 by the Cyclopentapeptide Cilengitide: Significance of the Guanidine Group and Accompanying Spectral Changes
نویسندگان
چکیده
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN (M.B., F.P.G.); Merck-Serono, RBM S.p.A. Instituto di Ricerche Biomediche A. Marxer, Colleretto Giacosa, TO, Italy (L.B., S.R.); Merck-Serono, Global Early Development, Darmstadt, Germany (H.D.); and Merck-Serono, Global Early Development, Darmstadt/Global DMPK, Grafing, Germany (A.F., D.G.) DMD Fast Forward. Published on July 1, 2014 as doi:10.1124/dmd.114.059295
منابع مشابه
Dmd059295 1438..1446
Cilengitide is a stable cyclic pentapeptide containing an Arg-GlyAsp motif responsible for selective binding to aVb3 and aVb5 integrins. The candidate drug showed unexpected inhibition of cytochrome P450 (P450) 3A4 at high concentrations, that is, a 15-mM concentration caused attenuation of P450 3A4 activity (depending on the probe substrate): 15–19% direct inhibition, 10–23% time-dependent inh...
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