PT  - JOURNAL ARTICLE
AU  - Zsuzsanna Rajnai
AU  - Dóra Méhn
AU  - Erzsébet Beéry
AU  - Alper Okyar
AU  - Márton Jani
AU  - Gábor K. Tóth
AU  - Ferenc Fülöp
AU  - Francis Lévi
AU  - Peter Krajcsi
TI  - ATP-Binding Cassette B1 Transports Seliciclib (<em>R</em>-Roscovitine), a Cyclin-Dependent Kinase Inhibitor
AID  - 10.1124/dmd.110.032805
DP  - 2010 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 2000--2006
VI  - 38
IP  - 11
4099  - http://dmd.aspetjournals.org/content/38/11/2000.short
4100  - http://dmd.aspetjournals.org/content/38/11/2000.full
SO  - Drug Metab Dispos2010 Nov 01; 38
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.