Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4
Joint Authors
Liu, Chenchang
Zhang, Jinghui
You, Guofeng
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-02-28
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Human organic anion transporter 4 (hOAT4) belongs to a family of multispecific organic anion transporters that play critical roles in the disposition of numerous drugs and therefore are the major sites for drug-drug interaction.
Drug-drug interactions contribute significantly to the individual variation in drug response.
hOAT4 is expressed in the kidney and placenta.
In the current study, we examined the interaction of 36 anticancer drugs with hOAT4 in kidney COS-7 cells and placenta BeWo cells.
Among the drugs tested, only epirubicin hydrochloride and dabrafenib mesylate exhibited > 50% cis-inhibitory effect, in COS-7 cells, on hOAT4-mediated uptake of estrone sulfate, a prototypical substrate for the transporter.
The IC50 values for epirubicin hydrochloride and dabrafenib mesylate were 5.24±0.95 μM and 8.30±3.30 μM, respectively.
Dixon plot analysis revealed that inhibition by epirubicin hydrochloride was noncompetitive with a Ki = 3 μM whereas inhibition by dabrafenib mesylate was competitive with a Ki = 4.26 μM.
Our results established that epirubicin hydrochloride and dabrafenib mesylate are inhibitors of hOAT4.
Furthermore, by comparing our data with clinically relevant exposures of these drugs, we conclude that although the tendency for dabrafenib mesylate to cause drug-drug interaction through hOAT4 is insignificant in the kidney, the propensity for epirubicin hydrochloride to cause drug-drug interaction is high.
American Psychological Association (APA)
Liu, Chenchang& Zhang, Jinghui& You, Guofeng. 2019. Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4. Journal of Oncology،Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1183997
Modern Language Association (MLA)
Liu, Chenchang…[et al.]. Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4. Journal of Oncology No. 2019 (2019), pp.1-8.
https://search.emarefa.net/detail/BIM-1183997
American Medical Association (AMA)
Liu, Chenchang& Zhang, Jinghui& You, Guofeng. Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4. Journal of Oncology. 2019. Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1183997
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1183997