Inhibitory effects of chemotherapeutics on human organic anion transporter hOAT4

May Fern Toh, Wonmo Suh, Haoxun Wang, Peter Zhou, Longqin Hu, Guofeng You

Research output: Contribution to journalArticle

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Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters which play critical roles in the body disposition of clinically important drugs. hOAT4 is expressed in the kidney and placenta. In the current study, we examined the inhibitory effects of 101 anticancer drugs from a clinical drug library on hOAT4 transport activity. The studies were carried out in hOAT4-expressing human kidney HEK-293 cells and human placenta BeWo cells. Among these drugs, only chlorambucil and cabazitaxel demonstrated more than 50% cis-inhibitory effect on hOAT4-mediated uptake of 3H-labeled estrone sulfate, a prototypical substrate for the transporter. The IC50 values for chlorambucil and cabazitaxel were 44.28 and 3.5 μM respectively. Dixon plot analysis revealed that inhibition by chlorambucil was competitive with a Ki = 55.73 μM whereas inhibition by cabazitaxel was non-competitive with a Ki = 1.78 μM. Our results demonstrated that chlorambucil and cabazitaxel were inhibitors of hOAT4. Furthermore, by comparing our data with clinically relevant exposures of these drugs, we conclude that the propensity for chlorambucil and cabazitaxel to cause drug-drug interaction through inhibition of hOAT4 is low.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalInternational Journal of Biochemistry and Molecular Biology
Issue number1
StatePublished - Jan 1 2016


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


  • Chemotherapeutics
  • Drug transporter
  • Organic anion transporter

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