Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1-and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions

被引：71
|
作者：
Alam, Khondoker [1 ]
Crowe, Alexandra [1 ]
Wang, Xueying [2 ]
Zhang, Pengyue [2 ]
Ding, Kai [3 ]
Li, Lang [2 ,4 ]
Yue, Wei [1 ]
机构：
[1] Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73117 USA
[2] Indiana Univ Sch Med, Dept Med & Mol Genet, Indiana Inst Personalized Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Biostat & Epidemiol, Oklahoma City, OK 73126 USA
[4] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 03期
关键词：
OATP1B1; OATP1B3; transcription; post-translation; protein degradation; lysosome inhibitor; proteasome inhibitor; UBIQUITIN-PROTEASOME SYSTEM; PROTEIN-KINASE-C; CANCER-SPECIFIC VARIANT; AMINO-ACID-RESIDUES; HEPATIC-UPTAKE; IN-VITRO; REDUCTASE INHIBITORS; SLCO1B1; POLYMORPHISM; 1B3; OATP1B3; ROSUVASTATIN PHARMACOKINETICS;
D O I：
10.3390/ijms19030855
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics. Growing evidences suggest that the transport function of OATP1B1 and OATP1B3 can be regulated at various levels such as genetic variation, transcriptional and post-translational regulation. The present review summarizes the up to date information on the regulation of OATP1B1 and OATP1B3 transport function at different levels with a focus on potential impact on OATP-mediated DDIs.
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页数：20
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