PT  - JOURNAL ARTICLE
AU  - Lora D. Weidner
AU  - Sami S. Zoghbi
AU  - Shuiyu Lu
AU  - Suneet Shukla
AU  - Suresh V. Ambudkar
AU  - Victor W. Pike
AU  - Jan Mulder
AU  - Michael M. Gottesman
AU  - Robert B. Innis
AU  - Matthew D Hall
TI  - The inhibitor Ko143 is not specific for ABCG2
AID  - 10.1124/jpet.115.225482
DP  - 2015 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.115.225482
4099  - http://jpet.aspetjournals.org/content/early/2015/07/07/jpet.115.225482.short
4100  - http://jpet.aspetjournals.org/content/early/2015/07/07/jpet.115.225482.full
AB  - Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143, a non-toxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2, although its specificity in mouse and human systems is unclear. This study examined the selectivity of Ko143 using human embryonic kidney cell lines transfected with ABCG2, ABCB1, or ABCC1 in several in vitro assays. The stability of Ko143 in rat plasma was measured using high performance liquid chromatography. Our results show that in addition to being a potent inhibitor of ABCG2, at higher concentrations (≥ 1 μM) Ko143 also has an effect on the transport activity of both ABCB1 and ABCC1. Furthermore, Ko143 was found to be unstable in rat plasma. These findings indicate that Ko143 lacks specificity for ABCG2 and should be taken into consideration when using Ko143 for both in vitro and in vivo experiments.