ATP-Binding Cassette B1 Transports Seliciclib (R-Roscovitine), a Cyclin-Dependent Kinase Inhibitor

作者：Rajnai Zsuzsanna; Mehn Dora; Beery Erzsebet; Okyar Alper; Jani Marton; Toth Gabor K; Fueloep Ferenc; Levi Francis; Krajcsi Peter^*

来源：Drug Metabolism and Disposition, 2010, 38(11): 2000-2006.

DOI：10.1124/dmd.110.032805

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 EC(50) of 4.2 mu M 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.

• 出版日期2010-11