PMID- 26893303
OWN - NLM
STAT- MEDLINE
DCOM- 20160815
LR  - 20220129
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 89
IP  - 5
DP  - 2016 May
TI  - Generation and Characterization of a Breast Cancer Resistance Protein Humanized 
      Mouse Model.
PG  - 492-504
LID - 10.1124/mol.115.102079 [doi]
AB  - Breast cancer resistance protein (BCRP) is expressed in various tissues, such as 
      the gut, liver, kidney and blood brain barrier (BBB), where it mediates the 
      unidirectional transport of substrates to the apical/luminal side of polarized 
      cells. Thereby BCRP acts as an efflux pump, mediating the elimination or 
      restricting the entry of endogenous compounds or xenobiotics into tissues and it 
      plays important roles in drug disposition, efficacy and safety. Bcrp knockout 
      mice (Bcrp(-/-)) have been used widely to study the role of this transporter in 
      limiting intestinal absorption and brain penetration of substrate compounds. Here 
      we describe the first generation and characterization of a mouse line humanized 
      for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon 
      was replaced with the corresponding human genomic region, such that the human 
      transporter is expressed under control of the murineBcrppromoter. We demonstrate 
      robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP 
      mice and the absence of major compensatory changes in the expression of other 
      genes involved in drug metabolism and disposition. Pharmacokinetic and brain 
      distribution studies with several BCRP probe substrates confirmed the functional 
      activity of the human transporter in these mice. Furthermore, we provide 
      practical examples for the use of hBCRP mice to study drug-drug interactions 
      (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human 
      BCRP in limiting absorption and BBB penetration of substrate compounds and to 
      investigate clinically relevant DDIs involving BCRP.
CI  - Copyright (c) 2016 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Dallas, Shannon
AU  - Dallas S
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Salphati, Laurent
AU  - Salphati L
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.) salphati.laurent@gene.com.
FAU - Gomez-Zepeda, David
AU  - Gomez-Zepeda D
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Wanek, Thomas
AU  - Wanek T
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Chen, Liangfu
AU  - Chen L
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Chu, Xiaoyan
AU  - Chu X
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Kunta, Jeevan
AU  - Kunta J
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Mezler, Mario
AU  - Mezler M
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Menet, Marie-Claude
AU  - Menet MC
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Chasseigneaux, Stephanie
AU  - Chasseigneaux S
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Decleves, Xavier
AU  - Decleves X
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Langer, Oliver
AU  - Langer O
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Pierre, Esaie
AU  - Pierre E
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - DiLoreto, Karen
AU  - DiLoreto K
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Hoft, Carolin
AU  - Hoft C
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Laplanche, Loic
AU  - Laplanche L
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Pang, Jodie
AU  - Pang J
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Pereira, Tony
AU  - Pereira T
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Andonian, Clara
AU  - Andonian C
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Simic, Damir
AU  - Simic D
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Rode, Anja
AU  - Rode A
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Yabut, Jocelyn
AU  - Yabut J
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Zhang, Xiaolin
AU  - Zhang X
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
FAU - Scheer, Nico
AU  - Scheer N
AD  - DMPK and Bioanalytical Research, Abbvie Deutschland GmbH & Co. KG, Ludwigshafen, 
      Germany (M.M., C.H., L.L.); Drug Metabolism and Pharmacokinetics, Genentech, 
      Inc., South San Francisco, CA (L.S., J.P., X.Z.); Drug Metabolism and 
      Pharmacokinetics, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 
      (L.C., C.A., E.P.); Health and Environment Department, AIT Austrian Institute of 
      Technology GmbH, Seibersdorf, Austria (T.W., O.L.); Department of Clinical 
      Pharmacology, Medical University of Vienna, Vienna, Austria (O.L.), Preclinical 
      Development and Safety, Janssen Research and Development, LLC, Spring House, PA 
      (S.D., J.K., K.D., D.S.). Merck Sharp and Dohme Corporation, Whitehouse Station, 
      New Jersey (X.C., T.P., J.Y.); Universite Paris Descartes, UMR-S 1144, Paris, 
      France (D.G.-Z., M.-C.M., S.C., X.D.); Taconic Biosciences GmbH, Koeln, Germany 
      (A.R., N.S.).
LA  - eng
GR  - P 24894/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160218
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abcg2 protein, mouse)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Xenobiotics)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/antagonists & 
      inhibitors/chemistry/genetics/*metabolism
MH  - Animals
MH  - Biological Availability
MH  - Biotransformation/drug effects
MH  - Blood-Brain Barrier/drug effects/metabolism
MH  - Drug Interactions
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knock-In Techniques
MH  - Humans
MH  - Intestinal Absorption/drug effects
MH  - Male
MH  - Membrane Transport Modulators/blood/metabolism/pharmacokinetics/pharmacology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism
MH  - Promoter Regions, Genetic/drug effects
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Tissue Distribution/drug effects
MH  - Xenobiotics/blood/metabolism/*pharmacokinetics/pharmacology
EDAT- 2016/02/20 06:00
MHDA- 2016/08/16 06:00
CRDT- 2016/02/20 06:00
PHST- 2015/10/14 00:00 [received]
PHST- 2016/02/17 00:00 [accepted]
PHST- 2016/02/20 06:00 [entrez]
PHST- 2016/02/20 06:00 [pubmed]
PHST- 2016/08/16 06:00 [medline]
AID - mol.115.102079 [pii]
AID - 10.1124/mol.115.102079 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2016 May;89(5):492-504. doi: 10.1124/mol.115.102079. Epub 2016 Feb 
      18.