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    P-glycoprotein

    P-glycoprotein 1 (permeability glycoprotein, abbrevi-

    ated as P-gp or Pgp) also known as multidrug resis-

    tance protein 1(MDR1) orATP-binding cassette sub-

    family B member 1 (ABCB1) orcluster of differenti-

    ation 243 (CD243) is an important protein of the cell

    membrane that pumps many foreign substances out of

    cells. More formally, it is anATP-dependent efflux pump

    with broad substrate specificity. It exists in animals, fungi

    and bacteria and likely evolved as a defense mechanism

    against harmful substances.

    P-gp is extensively distributed and expressed in theintestinal epitheliumwhere it pumpsxenobiotics(such as

    toxins or drugs) back into the intestinal lumen, inliver

    cells where it pumps them into bile ducts, in the cells

    of the proximal tubule of the kidney where it pumps

    them into urine-conducting ducts, and in the capillary

    endothelialcells composing thebloodbrain barrierand

    blood-testis barrier, where it pumps them back into the

    capillaries. Somecancercells also express large amounts

    of P-gp, which renders these cancers multi-drug resistant.

    P-gp is a glycoprotein that in humans is encoded by

    the ABCB1 gene.[2] P-gp is a well-characterizedABC-

    transporter (which transports a wide variety of sub-strates across extra- and intracellular membranes) of the

    MDR/TAPsubfamily.[3]

    P-gp was discovered in 1971 byVictor Ling.

    1 Function

    The protein belongs to the superfamily of ATP-binding

    cassette (ABC) transporters. ABC proteins transport

    various molecules across extra- and intra-cellular mem-

    branes. ABC genes are divided into seven distinctsubfamilies (ABC1, MDR/TAP, MRP, ALD, OABP,

    GCN20, White). This protein is a member of the

    MDR/TAP subfamily. Members of the MDR/TAP sub-

    family are involved inmultidrug resistance. P-gp is an

    ATP-dependent drug efflux pump for xenobiotic com-

    pounds with broad substrate specificity. It is responsible

    for decreased drug accumulation in multidrug-resistant

    cells and often mediates the development of resistance to

    anticancer drugs. This protein also functions as a trans-

    porter in thebloodbrain barrier.[4]

    P-gp transports various substrates across the cell mem-

    brane including:

    Drugs such ascolchicine, tacrolimusandquinidine

    Chemotherapeutic agents such as etoposide,

    doxorubicin, andvinblastine

    Lipids

    Steroids

    Xenobiotics

    Peptides

    Bilirubin

    Cardiac glycosideslikedigoxin

    Immunosuppressive agents

    Glucocorticoidslikedexamethasone

    HIV-type 1 antiretroviral therapy agents like

    protease inhibitorsand nonnucleoside reverse tran-

    scriptase inhibitors.

    Its ability to transport the above substrates accounts for

    the many roles of P-gp including:

    Regulating the distribution and bioavailability ofdrugs

    Increased intestinal expression of P-

    glycoprotein can reduce the absorption

    of drugs that are substrates for P-glycoprotein.

    Thus, there is a reduced bioavailability, and

    therapeutic plasma concentrations are not

    attained. On the other hand, supratherapeutic

    plasma concentrations and drug toxicity may

    result because of decreased P-glycoprotein

    expression

    Active cellular transportof antineoplasticsre-sulting inmultidrug resistanceto these drugs

    The removal of toxic metabolites and xenobiotics

    from cells intourine, bile, and the intestinal lumen

    The transport of compounds out of thebrainacross

    thebloodbrain barrier

    Digoxin uptake

    Prevention ofivermectinandloperamideentry into

    thecentral nervous system

    The migration ofdendritic cells

    Protection of hematopoietic stem cells from

    toxins.[3]

    1

    https://en.wikipedia.org/wiki/Stem_cellshttps://en.wikipedia.org/wiki/Dendritic_cellshttps://en.wikipedia.org/wiki/Central_nervous_systemhttps://en.wikipedia.org/wiki/Loperamidehttps://en.wikipedia.org/wiki/Ivermectinhttps://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttps://en.wikipedia.org/wiki/Brainhttps://en.wikipedia.org/wiki/Urinehttps://en.wikipedia.org/wiki/Multidrug_resistancehttps://en.wikipedia.org/wiki/Antineoplastichttps://en.wikipedia.org/wiki/Active_transporthttps://en.wikipedia.org/wiki/Gene_expressionhttps://en.wikipedia.org/wiki/NNRTI#Non-nucleoside_reverse_transcriptase_inhibitors_(NNRTIs)https://en.wikipedia.org/wiki/NNRTI#Non-nucleoside_reverse_transcriptase_inhibitors_(NNRTIs)https://en.wikipedia.org/wiki/Protease_inhibitorshttps://en.wikipedia.org/wiki/Dexamethasonehttps://en.wikipedia.org/wiki/Glucocorticoidhttps://en.wikipedia.org/wiki/Immunosuppressive_agentshttps://en.wikipedia.org/wiki/Digoxinhttps://en.wikipedia.org/wiki/Cardiac_glycosidehttps://en.wikipedia.org/wiki/Bilirubinhttps://en.wikipedia.org/wiki/Peptideshttps://en.wikipedia.org/wiki/Xenobiotichttps://en.wikipedia.org/wiki/Steroidshttps://en.wikipedia.org/wiki/Lipidshttps://en.wikipedia.org/wiki/Vinblastinehttps://en.wikipedia.org/wiki/Doxorubicinhttps://en.wikipedia.org/wiki/Etoposidehttps://en.wikipedia.org/wiki/Quinidinehttps://en.wikipedia.org/wiki/Tacrolimushttps://en.wikipedia.org/wiki/Colchicinehttps://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttps://en.wikipedia.org/wiki/Xenobiotichttps://en.wikipedia.org/wiki/Multidrug_resistancehttps://en.wikipedia.org/wiki/Victor_Linghttps://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttps://en.wikipedia.org/wiki/Multidrug_resistancehttps://en.wikipedia.org/wiki/ABC-transporterhttps://en.wikipedia.org/wiki/ABC-transporterhttps://en.wikipedia.org/wiki/Genehttps://en.wikipedia.org/wiki/Glycoproteinhttps://en.wikipedia.org/wiki/Antineoplastic_resistancehttps://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Blood-testis_barrierhttps://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttps://en.wikipedia.org/wiki/Endotheliumhttps://en.wikipedia.org/wiki/Capillaryhttps://en.wikipedia.org/wiki/Renal_tubuleshttps://en.wikipedia.org/wiki/Bile_ducthttps://en.wikipedia.org/wiki/Hepatocytehttps://en.wikipedia.org/wiki/Hepatocytehttps://en.wikipedia.org/wiki/Lumen_(biology)https://en.wikipedia.org/wiki/Xenobiotichttps://en.wikipedia.org/wiki/Intestinal_epitheliumhttps://en.wikipedia.org/wiki/Substrate_(biochemistry)https://en.wikipedia.org/wiki/Efflux_(microbiology)https://en.wikipedia.org/wiki/Adenosine_triphosphatehttps://en.wikipedia.org/wiki/Cell_membranehttps://en.wikipedia.org/wiki/Cell_membrane
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    2 7 REFERENCES

    It is inhibited by many drugs, such as:[5]

    Amiodarone

    Azithromycin

    Captopril

    Clarithromycin

    Cyclosporine

    Piperine

    Quercetin

    Quinidine

    Quinine

    Reserpine

    Ritonavir

    Tariquidar

    Verapamil

    2 Structure

    P-gp is a 170 kDa transmembrane glycoprotein, which

    includes 10-15 kDa of N-terminal glycosylation. The N-

    terminal half of the molecule contains 6 transmembrane

    domains, followed by a large cytoplasmic domain with an

    ATP-binding site, and then a second section with 6 trans-

    membrane domains and an ATP-binding site that shows

    over 65% of amino acid similarity with the first half of

    the polypeptide.[6] In 2009, the first structure of a mam-

    malian P-glycoprotein was solved (3G5U).[7] The struc-

    ture was derived from the mouse MDR3 gene product

    heterologously expressed in Pichia pastoris yeast. The

    structure of mouse P-gp is similar to structures of the bac-

    terial ABC transporter MsbA (3B5W and 3B5X)[8] that

    adopt an inward facing conformation that is believed to be

    important for binding substrate along the inner leaflet of

    the membrane. Additional structures (3G60 and 3G61)

    of P-gp were also solved revealing the binding site(s)

    of two different cyclic peptide substrate/inhibitors. The

    promiscuous binding pocket of P-gp is lined with aro-

    matic amino acid side chains. However, the murine P-gp

    structure is incomplete, missing an intermediate linker

    sequence proved to be essential for substrate recogni-

    tion and ATP hydrolysis. Through Molecular Dynamic

    (MD) simulations, this sequence was proved to have a di-

    rect impact in the transporters structural stability (in thenucleotide-binding domains) and defining a lower bound-

    ary for the internal drug-binding pocket.[9]

    3 Mechanism of action

    Substrate enters P-gp either from an opening within the

    inner leaflet of the membraneor from an opening at the

    cytoplasmic side of the protein. ATP binds at the cyto-

    plasmic side of the protein. Following binding of each,

    ATP hydrolysis shifts the substrate into a position to be

    excreted from the cell. Release of the phosphate (from

    the original ATP molecule) occurs concurrently with sub-

    strate excretion. ADP is released, and a new molecule of

    ATP binds to the secondary ATP-binding site. Hydroly-

    sis and release of ADP and a phosphate molecule resets

    the protein, so that the process can start again.

    4 Tissue distribution

    P-gp is expressed primarily in certain cell types in the

    liver,pancreas,kidney,colon, andjejunum.[10]

    5 Detecting the activity of the

    transporter

    The activity of the transporter can be determined by both

    membraneATPaseand cellularcalceinassays.

    Radioactive verapamil can be used for measuring P-gp

    function withpositron emission tomography.[11]

    P-gp is also used to differentiate transitionalB-cellsfromnaive B-cells. Dyes such as Rhodamine123 and Mito-

    Tracker Dyes from Invitrogen can be used to make this

    differentiation.[12]

    6 History

    P-gp was first cloned and characterized in 1976. It was

    shown to be responsible for conferring multidrug resis-

    tance upon mutant cultured cancer cells that had devel-

    oped resistance to cytotoxic drugs.[3][13]

    The structure of P-gp was resolved byx-ray crystallogra-

    phyin 2009.[7]

    7 References

    [1] PDB 3G60; Aller SG, Yu J, Ward A, Weng Y, Chit-

    taboina S, Zhuo R, Harrell PM, Trinh YT, Zhang

    Q, Urbatsch IL, Chang G (March 2009). Structure

    of P-glycoprotein reveals a molecular basis for poly-

    specific drug binding. Science 323 (5922): 171822.

    doi:10.1126/science.1168750. PMC 2720052. PMID

    19325113.[2] Ueda K, Clark DP, Chen CJ, Roninson IB,Gottesman

    MM, Pastan I (January 1987). The human multidrug

    http://www.jbc.org/cgi/content/abstract/262/2/505https://en.wikipedia.org/wiki/Michael_M._Gottesmanhttps://en.wikipedia.org/wiki/Michael_M._Gottesmanhttps://www.ncbi.nlm.nih.gov/pubmed/19325113https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052https://en.wikipedia.org/wiki/PubMed_Centralhttps://dx.doi.org/10.1126%252Fscience.1168750https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052http://www.rcsb.org/pdb/explore/explore.do?structureId=3G60https://en.wikipedia.org/wiki/Protein_Data_Bankhttps://en.wikipedia.org/wiki/X-ray_crystallographyhttps://en.wikipedia.org/wiki/X-ray_crystallographyhttps://en.wikipedia.org/wiki/B_cellhttps://en.wikipedia.org/wiki/Positron_emission_tomographyhttps://en.wikipedia.org/wiki/Verapamilhttps://en.wikipedia.org/wiki/Calceinhttps://en.wikipedia.org/wiki/ATPase_assayhttps://en.wikipedia.org/wiki/Jejunumhttps://en.wikipedia.org/wiki/Colon_(anatomy)https://en.wikipedia.org/wiki/Kidneyhttps://en.wikipedia.org/wiki/Pancreashttps://en.wikipedia.org/wiki/Liverhttps://en.wikipedia.org/wiki/Lipid_bilayerhttps://en.wikipedia.org/wiki/Glycoproteinhttps://en.wikipedia.org/wiki/Verapamilhttps://en.wikipedia.org/wiki/Tariquidarhttps://en.wikipedia.org/wiki/Ritonavirhttps://en.wikipedia.org/wiki/Reserpinehttps://en.wikipedia.org/wiki/Quininehttps://en.wikipedia.org/wiki/Quinidinehttps://en.wikipedia.org/wiki/Quercetinhttps://en.wikipedia.org/wiki/Piperinehttps://en.wikipedia.org/wiki/Cyclosporinehttps://en.wikipedia.org/wiki/Clarithromycinhttps://en.wikipedia.org/wiki/Captoprilhttps://en.wikipedia.org/wiki/Azithromycinhttps://en.wikipedia.org/wiki/Amiodarone
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    3

    resistance (mdr1) gene. cDNA cloning and transcrip-

    tion initiation. J. Biol. Chem. 262 (2): 5058. PMID

    3027054.

    [3] Dean, Michael (2002-11-01).The Human ATP-Binding

    Cassette (ABC) Transporter Superfamily. National Li-

    brary of Medicine (US), NCBI. Retrieved 2008-03-02.

    [4] Entrez Gene: ABCB1.

    [5] Drug Development and Drug Interactions: Table of Sub-

    strates, Inhibitors and Inducers.

    [6] Franck Vigui (1998-03-01). ABCB1. Atlas of Genet-

    ics and Cytogenetics in Oncology and Haematology. Re-

    trieved 2008-03-02.

    [7] Stephen Aller; Jodie Yu, Andrew Ward, Yue Weng,

    Srinivas Chittaboina, Rupeng Zhuo, Patina M. Har-

    rell, Yenphuong T. Trinh,Qinghai Zhang, Ina L. Ur-

    batsch,Geoffrey Chang(2009-03-27). Structure of P-glycoprotein Reveals a Molecular Basis for Poly-Specific

    Drug Binding. Science (Science) 323 (5922): 1718

    1722. doi:10.1126/science.1168750. PMC 2720052.

    PMID 19325113. Retrieved 2009-04-12.

    [8] Ward A, Reyes CL, Yu J, Roth CB, Chang G (November

    2007). Flexibility in the ABC transporter MsbA: Alter-

    nating access with a twist. Proc. Natl. Acad. Sci. U.S.A.

    104 (48): 1900510. doi:10.1073/pnas.0709388104.

    PMC 2141898.PMID 18024585.

    [9] Ferreira RJ, Ferreira M-JU, dos Santos DJVA (May

    2012). Insights on P-Glycoproteins Efflux Mech-

    anism obtained by Molecular Dynamics Simula-

    tions. J Chem Theory Comput 8 (6): 18531864.

    doi:10.1021/ct300083m.

    [10] Thiebaut F, Tsuruo T, Hamada H,Gottesman MM, Pas-

    tan I, Willingham MC (November 1987). Cellular

    localization of the multidrug-resistance gene prod-

    uct P-glycoprotein in normal human tissues. Proc.

    Natl. Acad. Sci. U.S.A. 84 (21): 77358.

    doi:10.1073/pnas.84.21.7735. PMC 299375. PMID

    2444983.

    [11] Luurtsema G, Windhorst AD, Mooijer MPJ, Herscheid

    A, Lammertsma AA, Franssen EJF (2002). Fullyautomated high yield synthesis of (R)- and (S)-[C-

    11]verapamil for measuring P-glycoprotein function with

    positron emission tomography. Journal of Labelled

    Compounds & Radiopharmaceuticals 45 (14): 1199

    1207.doi:10.1002/jlcr.632.

    [12] Wirths S, Lanzavecchia A (December 2005). ABCB1

    transporter discriminates human resting naive B cells from

    cycling transitional and memory B cells. Eur. J. Im-

    munol. 35 (12): 343341. doi:10.1002/eji.200535364.

    PMID 16259010.

    [13] Juliano RL, Ling V (1976). A surface glycoprotein mod-

    ulating drug permeability in Chinese hamster ovary cellmutants. Biochim. Biophys. Acta 455 (1): 15262.

    doi:10.1016/0005-2736(76)90160-7.PMID 990323.

    8 Further reading

    Ling V (1997). Multidrug resistance: molecu-

    lar mechanisms and clinical relevance. Cancer

    Chemother. Pharmacol. 40 Suppl (7): S38.

    doi:10.1007/s002800051053.PMID 9272126.

    Kerb R, Hoffmeyer S, Brinkmann U (2001).

    ABC drug transporters: hereditary polymorphisms

    and pharmacological impact in MDR1, MRP1

    and MRP2. Pharmacogenomics 2 (1): 5164.

    doi:10.1517/14622416.2.1.51.PMID 11258197.

    Akiyama S (2002). "[Mechanisms of drug resis-

    tance and reversal of the resistance]". Hum. Cell

    14 (4): 25760.PMID 11925925.

    Brinkmann U (2002). Functional polymorphisms

    of the human multidrug resistance (MDR1) gene:correlation with P glycoprotein expression and activ-

    ity in vivo. Novartis Found. Symp. Novartis Foun-

    dation Symposia 243: 20710; discussion 2102,

    2315.doi:10.1002/0470846356.ch15.ISBN 978-

    0-470-84635-3.PMID 11990778.

    Vradi A, Szakcs G, Bakos E, Sarkadi B (2002).

    P glycoprotein and the mechanism of multidrug re-

    sistance. Novartis Found. Symp. Novartis Founda-

    tion Symposia 243: 5465; discussion 658, 1805.

    doi:10.1002/0470846356.ch5. ISBN 978-0-470-

    84635-3.PMID 11990782.

    Hegedus T, Orfi L, Seprodi A, et al. (2002).

    Interaction of tyrosine kinase inhibitors with the

    human multidrug transporter proteins, MDR1 and

    MRP1. Biochim. Biophys. Acta1587(23): 318

    25. doi:10.1016/s0925-4439(02)00095-9. PMID

    12084474.

    Pallis M, Turzanski J, Higashi Y, Russell N (2003).

    P-glycoprotein in acute myeloid leukaemia: ther-

    apeutic implications of its association with both a

    multidrug-resistant and an apoptosis-resistant phe-

    notype. Leuk. Lymphoma 43 (6): 1221

    8. doi:10.1080/10428190290026277. PMID

    12152989.

    Schaich M, Illmer T (2003). Mdr1 gene ex-

    pression and mutations in Ras proto-oncogenes in

    acute myeloid leukemia. Leuk. Lymphoma 43

    (7): 134554. doi:10.1080/10428190290033279.

    PMID 12389613.

    Fromm MF (2003). The influence of MDR1 poly-

    morphisms on P-glycoprotein expression and func-

    tion in humans. Adv. Drug Deliv. Rev. 54 (10):1295310. doi:10.1016/S0169-409X(02)00064-9.

    PMID 12406646.

    https://www.ncbi.nlm.nih.gov/pubmed/12406646https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1016%252FS0169-409X%252802%252900064-9https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/12389613https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1080%252F10428190290033279https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/12152989https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1080%252F10428190290026277https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/12084474https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1016%252Fs0925-4439%252802%252900095-9https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/11990782https://en.wikipedia.org/wiki/PubMed_Identifierhttps://en.wikipedia.org/wiki/Special:BookSources/978-0-470-84635-3https://en.wikipedia.org/wiki/Special:BookSources/978-0-470-84635-3https://en.wikipedia.org/wiki/International_Standard_Book_Numberhttps://dx.doi.org/10.1002%252F0470846356.ch5https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/11990778https://en.wikipedia.org/wiki/PubMed_Identifierhttps://en.wikipedia.org/wiki/Special:BookSources/978-0-470-84635-3https://en.wikipedia.org/wiki/Special:BookSources/978-0-470-84635-3https://en.wikipedia.org/wiki/International_Standard_Book_Numberhttps://dx.doi.org/10.1002%252F0470846356.ch15https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/11925925https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pubmed/11258197https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1517%252F14622416.2.1.51https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/9272126https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1007%252Fs002800051053https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/990323https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1016%252F0005-2736%252876%252990160-7https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/16259010https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1002%252Feji.200535364https://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1002%252Fjlcr.632https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/2444983https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC299375https://en.wikipedia.org/wiki/PubMed_Centralhttps://dx.doi.org/10.1073%252Fpnas.84.21.7735https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC299375https://www.ncbi.nlm.nih.gov/pmc/articles/PMC299375https://www.ncbi.nlm.nih.gov/pmc/articles/PMC299375https://en.wikipedia.org/wiki/Michael_M._Gottesmanhttps://dx.doi.org/10.1021%252Fct300083mhttps://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/18024585https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141898https://en.wikipedia.org/wiki/PubMed_Centralhttps://dx.doi.org/10.1073%252Fpnas.0709388104https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141898https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141898https://www.ncbi.nlm.nih.gov/pubmed/19325113https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052https://en.wikipedia.org/wiki/PubMed_Centralhttps://dx.doi.org/10.1126%252Fscience.1168750https://en.wikipedia.org/wiki/Digital_object_identifierhttp://www.sciencemag.org/cgi/content/abstract/323/5922/1718http://www.sciencemag.org/cgi/content/abstract/323/5922/1718http://www.sciencemag.org/cgi/content/abstract/323/5922/1718https://en.wikipedia.org/wiki/Geoffrey_Changhttp://atlasgeneticsoncology.org//Genes/PGY1ID105.htmlhttp://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htmhttp://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htmhttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5243http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mono_001.chapter.137http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mono_001.chapter.137https://www.ncbi.nlm.nih.gov/pubmed/3027054https://en.wikipedia.org/wiki/PubMed_Identifierhttp://www.jbc.org/cgi/content/abstract/262/2/505http://www.jbc.org/cgi/content/abstract/262/2/505
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    9 External links

    P-Glycoprotein at the US National Library of

    MedicineMedical Subject Headings(MeSH)

    Jessica R Oesterheld (2002-05-01). P-

    glycoprotein. Mental Health Connections,

    Inc. Archived from the originalon 2008-02-07.Retrieved 2008-03-02.

    P-glycoprotein substrate prediction

    NextBio.com

    PharmGKB.org

    The role of MDR1-MDCK in permeability studies

    The performance of MDR1-MDCK permeability

    studies for P-glycoprotein substrate identification.

    ABCB1human gene location in theUCSC Genome

    Browser.

    ABCB1 human gene details in the UCSC Genome

    Browser.

    This article incorporates text from the United States Na-

    tional Library of Medicine, which is in thepublic domain.

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