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dc.contributor.authorDurmus S.en_US
dc.contributor.authorvan Hoppe S.en_US
dc.contributor.authorSchinkel A.H.en_US
dc.date.accessioned2018-04-12T10:55:36Z
dc.date.available2018-04-12T10:55:36Z
dc.date.issued2016en_US
dc.identifier.issn13687646
dc.identifier.urihttp://hdl.handle.net/11693/36854
dc.description.abstractIt is now widely accepted that organic anion-transporting polypeptides (OATPs), especially members of the OATP1A/1B family, can have a major impact on the disposition and elimination of a variety of endogenous molecules and drugs. Owing to their prominent expression in the sinusoidal plasma membrane of hepatocytes, OATP1B1 and OATP1B3 play key roles in the hepatic uptake and plasma clearance of a multitude of structurally diverse anti-cancer and other drugs. Here, we present a thorough assessment of the currently available OATP1A and OATP1B knockout and transgenic mouse models as key tools to study OATP functions in vivo. We discuss recent studies using these models demonstrating the importance of OATPs, primarily in the plasma and hepatic clearance of anticancer drugs such as taxanes, irinotecan/SN-38, methotrexate, doxorubicin, and platinum compounds. We further discuss recent work on OATP-mediated drug–drug interactions in these mouse models, as well as on the role of OATP1A/1B proteins in the phenomenon of hepatocyte hopping, an efficient and flexible way of liver detoxification for both endogenous and exogenous substrates. Interestingly, glucuronide conjugates of both the heme breakdown product bilirubin and the protein tyrosine kinase-targeted anticancer drug sorafenib are strongly affected by this process. The clinical relevance of variation in OATP1A/1B activity in patients has been previously revealed by the effects of polymorphic variants and drug–drug interactions on drug toxicity. The development of in vivo tools to study OATP1A/1B functions has greatly advanced our mechanistic understanding of their functional role in drug pharmacokinetics, and their implications for therapeutic efficacy and toxic side effects of anticancer and other drug treatments. © 2016 Elsevier Ltden_US
dc.language.isoEnglishen_US
dc.source.titleDrug Resistance Updatesen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.drup.2016.06.005en_US
dc.subjectDrug dispositionen_US
dc.subjectDrug–drug interactionsen_US
dc.subjectHepatic uptakeen_US
dc.subjectOATP1A/1B transportersen_US
dc.subjectOATP1B1en_US
dc.subjectOATP1B3en_US
dc.subjectantineoplastic agenten_US
dc.subjectbilirubinen_US
dc.subjectbilirubin glucuronideen_US
dc.subjectcabazitaxelen_US
dc.subjectcarboplatinen_US
dc.subjectcarboxylesteraseen_US
dc.subjectcisplatinen_US
dc.subjectdocetaxelen_US
dc.subjectdoxorubicinen_US
dc.subjectfirtecanen_US
dc.subjectglucuronideen_US
dc.subjecthemeen_US
dc.subjectirinotecanen_US
dc.subjectmethotrexateen_US
dc.subjectorganic anion transporteren_US
dc.subjectoxaliplatinen_US
dc.subjectpaclitaxelen_US
dc.subjectprotein tyrosine kinaseen_US
dc.subjectprotein tyrosine kinase inhibitoren_US
dc.subjectrifampicinen_US
dc.subjectsolute carrier organic anion transporter 1Aen_US
dc.subjectsolute carrier organic anion transporter 1Ben_US
dc.subjectsolute carrier organic anion transporter 1B1en_US
dc.subjectsolute carrier organic anion transporter 1B3en_US
dc.subjectsorafeniben_US
dc.subjecttaxane derivativeen_US
dc.subjecttelmisartanen_US
dc.subjectunclassified drugen_US
dc.subjectantineoplastic agenten_US
dc.subjectcamptothecinen_US
dc.subjectcarbanilamide derivativeen_US
dc.subjectdoxorubicinen_US
dc.subjectirinotecanen_US
dc.subjectmethotrexateen_US
dc.subjectnicotinamideen_US
dc.subjectOatp1a1 protein, mouseen_US
dc.subjectorganic cation transporteren_US
dc.subjectplatinum derivativeen_US
dc.subjectSLCO1B1 protein, humanen_US
dc.subjectsolute carrier organic anion transporter 1B1en_US
dc.subjectsorafeniben_US
dc.subjecttaxoiden_US
dc.subjectArticleen_US
dc.subjectclinical assessmenten_US
dc.subjectDNA modificationen_US
dc.subjectdrug conjugationen_US
dc.subjectdrug cytotoxicityen_US
dc.subjectdrug detoxificationen_US
dc.subjectdrug dispositionen_US
dc.subjectdrug efficacyen_US
dc.subjectdrug mechanismen_US
dc.subjectdrug transporten_US
dc.subjectgenetically engineered mouse strainen_US
dc.subjecthepatic clearanceen_US
dc.subjecthumanen_US
dc.subjectin vitro studyen_US
dc.subjectin vivo studyen_US
dc.subjectknockout mouseen_US
dc.subjectliver cellen_US
dc.subjectnonhumanen_US
dc.subjectplasma clearanceen_US
dc.subjectpriority journalen_US
dc.subjectprotein blood levelen_US
dc.subjectprotein functionen_US
dc.subjecttherapy effecten_US
dc.subjecttransgenic mouseen_US
dc.subjectupregulationen_US
dc.subjectanalogs and derivativesen_US
dc.subjectanimalen_US
dc.subjectdeficiencyen_US
dc.subjectdrug effectsen_US
dc.subjectdrug inactivationen_US
dc.subjectdrug interactionen_US
dc.subjectgene expressionen_US
dc.subjectgeneticsen_US
dc.subjectliveren_US
dc.subjectmetabolismen_US
dc.subjectmouseen_US
dc.subjectneoplasmen_US
dc.subjectpathologyen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectCamptothecinen_US
dc.subjectDoxorubicinen_US
dc.subjectDrug Interactionsen_US
dc.subjectGene Expressionen_US
dc.subjectHepatocytesen_US
dc.subjectHumansen_US
dc.subjectInactivation, Metabolicen_US
dc.subjectLiveren_US
dc.subjectMethotrexateen_US
dc.subjectMiceen_US
dc.subjectMice, Transgenicen_US
dc.subjectNeoplasmsen_US
dc.subjectNiacinamideen_US
dc.subjectOrganic Cation Transport Proteinsen_US
dc.subjectPhenylurea Compoundsen_US
dc.subjectPlatinum Compoundsen_US
dc.subjectSolute Carrier Organic Anion Transporter Family Member 1b1en_US
dc.subjectTaxoidsen_US
dc.titleThe impact of Organic Anion-Transporting Polypeptides (OATPs) on disposition and toxicity of antitumor drugs: Insights from knockout and humanized miceen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage72en_US
dc.citation.epage88en_US
dc.citation.volumeNumber27en_US
dc.identifier.doi10.1016/j.drup.2016.06.005en_US
dc.publisherChurchill Livingstoneen_US


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