RT Journal Article SR Electronic T1 ATP-Binding Cassette B1 Transports Seliciclib (R-Roscovitine), a Cyclin-Dependent Kinase Inhibitor JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 2000 OP 2006 DO 10.1124/dmd.110.032805 VO 38 IS 11 A1 Zsuzsanna Rajnai A1 Dóra Méhn A1 Erzsébet Beéry A1 Alper Okyar A1 Márton Jani A1 Gábor K. Tóth A1 Ferenc Fülöp A1 Francis Lévi A1 Peter Krajcsi YR 2010 UL http://dmd.aspetjournals.org/content/38/11/2000.abstract AB Seliciclib, a cyclin-dependent kinase inhibitor, is a promising candidate to treat a variety of cancers. Pharmacokinetic studies have shown high oral bioavailability but limited brain exposure to the drug. This study shows that seliciclib is a high-affinity substrate of ATP-binding cassette B1 (ABCB1) because it activates the ATPase activity of the transporter with an EC50 of 4.2 μM and shows vectorial transport in MDCKII-MDR1 cells, yielding an efflux ratio of 8. This interaction may be behind the drug's limited penetration of the blood-brain barrier. ABCB1 overexpression, on the other hand, does not confer resistance to the drug in the models tested. These findings should be considered when treatment strategies using seliciclib are designed.