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P-Glycoprotein: A Critical Comparison of Models Depicting Mechanism of Drug Efflux and Role of Modulators


Permeability or P-glycoprotein (P-gp), present in both prokaryotes and eukaryotes is an essential protein belonging to the adenosine triphosphate (ATP) binding cassette transporter family. It functions as a protective barrier by extrusion of wide range of substrates including toxins, xenobiotic compounds and drugs from the cell. These are ubiquitous integral membrane proteins that have ATPase activity for substrate transport across the lipid membrane. The potential role of P-gp in efflux mechanism is to avoid drug accumulation and to provide intrinsic resistance to a broad range of anticancer compounds against sarcoma, breast cancer and certain types of leukemia. This review recapitulates the structural and functional aspects of core domains of P-gp. Furthermore, various proposed mechanisms of translocation of substrates across the membrane which explain the conformational changes in different domains upon ATP binding and hydrolysis. Another critical aspect focuses on different modulators and their mode of binding on P-gp which facilitates the inhibition of efflux mechanism. Ten models of drug efflux mechanism have been illustrated and a comparative account of their applicability and limitations given, paving way for further improvements. In the present study it has been observed that contrary to the earlier reported models where transmembrane domain is the preferred binding site of ligands resulting in their efflux through ATP hydrolysis at nucleotide binding domain (NBD) site. The more hydrophilic NBD appears to be the appropriate binding site for majority of the hydrophobic third and fourth generation modulators thus inhibiting the binding and hydrolysis of ATP resulting in inhibition of efflux.

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  1. 1.

    Linton KJ (2007) Structure and function of ABC transporters. Physiology 22:122–130

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Ma A, Wang C, Chen Y, Yuan W (2013) P-glycoprotein alters blood- brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy. Drug Des Dev Ther 7:1447–1454. doi:10.2147/DDDT.S52533

    Google Scholar 

  3. 3.

    Rosenberg MF, Kamis AB, Callaghan R, Higgins C, Ford RC (2003) Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding. J Biol Chem 278:8294–8299

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Rosenberg MF, Velarde G, Ford RC, Martin C, Berridge G, Kerr ID, Callaghan R, Schmidlin A, Wooding C, Linton KJ, Higgins CF (2001) Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO J 20(20):5615–5625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. 5.

    Oldham ML, Davidson AL, Chen J (2008) Structural insights into ABC transporter mechanism. Curr Opin Struct Biol 18(6):726–733. doi:10.1016/

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. 6.

    Singh DV, Godbole MM, Misra K (2013) A plausible explanation for enhanced bioavailability of P-gp substrates in presence of piperine: simulation for next generation of P-gp inhibitors. J Mol Model 19(1):227–238

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Altenberg GA (2003) The engine of ABC proteins. News Physiol Sci 18:191–195. doi:10.1007/s00894-012-1535-8

    CAS  PubMed  Google Scholar 

  8. 8.

    Rai V, Gaur M, Shukla S, Shukla S, Ambudkar SV, Komath SS, Prasad R (2006) Conserved Asp327 of walker B motif in the N-terminal nucleotide binding domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis. Biochemistry 45(49):14726–14739

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. 9.

    Procko E, O’Mara ML, Bennett WF, Tieleman DP, Gaudet R (2009) The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEB J 23(5):1287–1302. doi:10.1096/fj.08-121855

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Bakos E, Klein I, Welker E, Szabó K, Müller M, Sarkadi B, Váradi A (1997) Characterization of the human multidrug resistance protein containing mutations in the ATP-binding cassette signature region. Biochem J 323:777–783

    PubMed Central  CAS  PubMed  Google Scholar 

  11. 11.

    Zhang DW, Graf GA, Gerard RD, Cohen JC, Hobbs HH (2006) Functional asymmetry of nucleotide binding domains in ABCG5 and ABCG8. J Biol Chem 281(7):4507–4516

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Tombline G, Bartholomew L, Gimi K, Tyndall GA, Senior AE (2004) Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysis. J Biol Chem 279(7):5363–5373

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Aittoniemi J, de Wet H, Ashcroft FM, Sansom M (2010) Asymmetric switching in a homodimeric ABC transporter: a simulation study. PLoS Comput Biol 6(4):1–10. doi:10.1371/journal.pcbi.1000762

    Article  Google Scholar 

  14. 14.

    Sarkadi B, Homolya L, Szakacs G, Varadi A (2006) Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol Rev 86(4):1179–1236

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Prajapati R, Singh U, Patil A, Khomane KS, Bagul P, Bansal AK, Sangamwar AT (2013) In silico model for P-glycoprotein substrate prediction: insights from molecular dynamics and in vitro studies. J Comput Aided Mol Des 27(4):347–363. doi:10.1007/s10822-013-9650-x

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Wen PC, Verhalen B, Wilkens S, Mchaourab HS, Tajkhorshid E (2013) On the origin of large flexibility of P-glycoprotein in the inward-facing state. J Biol Chem 28(26):19211–19220. doi:10.1074/jbc.M113.450114

    Article  Google Scholar 

  17. 17.

    Ruysschaert JM (2005) Orientational and conformational changes in transmembrane domains of membrane proteins. Cell Mol Biol Lett 10, supplement

  18. 18.

    Van Veen HW, Higgins CF, Konings WN (2001) Molecular basis of multidrug transport by ATP-binding cassette transporters: a proposed two-cylinder engine model. J Mol Microbiol Biotechnol 3(2):185–192

    PubMed  Google Scholar 

  19. 19.

    Moody JE, Millen L, Binns D, Hunt JF, Thomas PJ (2002) Cooperative, ATP dependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporter. Biol Chem 277(24):21111–21114

    Article  CAS  Google Scholar 

  20. 20.

    Omote H, Al-Shawi MK (2006) Interaction of transported drugs with the lipid bilayer and P-glycoprotein through a solvation exchange mechanism. Biophys J 90(11):4046–4059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. 21.

    Sauna ZE, Ambudkar SV (2007) About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work. Mol Cancer Ther 6(1):13–23

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Sonne J, Kandt C, Peters GH, Hansen FY, Jensen M, Tieleman DP (2007) Simulation of the coupling between nucleotide binding and transmembrane domains in the ATP binding cassette transporter BtuCD. Biophys J 92(8):2727–2734

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. 23.

    Locher KP, Lee AT, Rees DC (2002) The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science 296(5570):1091–1098

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Lu G, Westbrooks JM, Davidson AL, Chen J (2005) ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation. Proc Natl Acad Sci USA 102(50):17969–17974

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. 25.

    Oliveira AS, Baptista AM, Soares CM (2010) Insights into the molecular mechanism of an ABC transporter: conformational changes in the NBD dimer of MJ0796. J Phys Chem B 114(16):5486–5496. doi:10.1021/jp905735y

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Stavri M, Piddock LJ, Gibbons S (2007) Bacterial efflux pump inhibitors from natural sources. J Antimicrob Chemother 59(6):1247–1260

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Thomas H, Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control 10(2):159–165

    PubMed  Google Scholar 

  28. 28.

    Wu CP, Ohnuma S, Ambudkar SV (2011) Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 12(4):609–620

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. 29.

    Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D, Plumb JA, Templeton D, Charlton P (2001) In vitro and in vivo reversal of P-glycoprotein- mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 61(2):749–758

    CAS  PubMed  Google Scholar 

  30. 30.

    Werle M (2008) Natural and synthetic polymers as inhibitors of drug efflux pumps. J Antimicrob Chemother 25(3):500–511

    CAS  Google Scholar 

  31. 31.

    Liu KCSC, Yang SL, Roberts MF, Elford BC, Phillipson JD (1992) Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures. Plant Cell Rep 11:637–640. doi:10.1007/BF00236389

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Ferreira JF, Luthria DL, Sasaki T, Heyerick A (2010) Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules 15(5):3135–3170. doi:10.3390/molecules15053135

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Stermitz FR, Cashman KK, Halligan KM, Morel C, Tegos GP, Lewis K (2003) Polyacylated neohesperidosides from Geranium caespitosum: bacterial multidrug resistance pump inhibitors. Bioorg Med Chem Lett 13:1915–1918

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Oluwatuyi M, Kaatz GW, Gibbons S (2004) Antibacterial and resistance modifying activity of Rosmarinus Officinalis. Phytochemistry 65:3249–3254

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Neyfakh AA, Bidnenko VE, Chen LB (1991) Efflux-mediated multi-drugresistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc Natl Acad Sci USA 88:4781–4785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. 36.

    Belofsky G, Carreno R, Lewis K, Ball A, Casadei G, Tegos GP (2006) Metabolites of the ‘smoke tree’, Dalea spinosa, potentiate antibiotic activity against multidrugresistant Staphylococcus aureus. J Nat Prod 69:261–264

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Gibbons S, Oluwatuyi M, Veitch N, Gray AI (2003) Bacterial resistance modifying agents from Lycopus europaeus. Phytochemistry 62:83–87

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Abulrob AN, Suller MTE, Gumbleton M, Simons C, Russell AD (2004) Identification and biological evaluation of grapefruit oil components as potential novel efflux pump modulators in methicillin-resistant Staphylococcus aureus bacterial strains. Phytochemistry 65:3021–3027

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Marquez B, Neuville L, Moreau NJ, Genet JP, dos Santos AF, Caño de Andrade MC, Sant’Ana AE (2005) Multidrug resistance reversal agent from Jatropha elliptica. Phytochemistry 66:1804–1811

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Lomovskaya O, Warren MS, Lee A, Galazzo J, Fronko R, Lee M, Blais J, Cho D, Chamberland S, Renau T, Leger R, Hecker S, Watkins W, Hoshino K, Ishida H, Lee VJ (2001) Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother 45(1):105–116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. 41.

    Falcão-Silva VS, Silva DA, Souza Mde F (2009) Modulation of drug resistance in Staphylococcus aureus by a kaempferol glycoside from Herissantia tiubae (Malvaceae). Phytother Res 23(10):1367–1370. doi:10.1002/ptr.2695

    Article  PubMed  Google Scholar 

  42. 42.

    Kesharwani RK, Misra K (2011) Prediction of binding site for curcuminoids at human topoisomerase II α protein; an in silico approach. Curr Sci 101(8):1060–1065

    CAS  Google Scholar 

  43. 43.

    Singh DB, Gupta MK, Kesharwani RK, Misra K (2013) Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targetingb-amyloid. Netw Model Anal Health Inform Bioinform 2(1):13–27

    Article  Google Scholar 

  44. 44.

    Tian QE, De Li H, Yan M (2012) Effects of Astragalus polysaccharides on P-glycoprotein efflux pump function and protein expression in H22 hepatoma cells in vitro. BMC Complement Altern Med 12:94. doi:10.1186/1472-6882-12-94

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. 45.

    Zhao BX, Sun YB, Wang SQ, Duan L, Huo QL, Ren F, Li GF (2013) Grape seed procyanidin reversal of p-glycoprotein associated multi-drug resistance via down-regulation of NF-κB and MAPK/ERK mediated YB-1 activity in A2780/T cells. PLoS One 8(8):e71071. doi:10.1371/journal.pone.0071071

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. 46.

    Callaghan R, Ford RC, Kerr ID (2006) The translocation mechanism of P-glycoprotein. FEBS Lett 580(4):1053–1063

    Article  Google Scholar 

  47. 47.

    Sharom FJ (1997) The P-glycoprotein efflux pump: how does it transport drugs? J Membr Biol 160(3):161–175

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Sharom FJ (2011) The P-glycoprotein multidrug transporter. Essays Biochem 50(1):161–178. doi:10.1042/bse0500161

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Jin MS, Oldham ML, Zhang Q, Chen J (2012) Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature 490(7421):566–569. doi:10.1038/nature11448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. 50.

    Ferreira RJ, Ferreira MJ, dos Santos DJ (2013) Molecular docking characterizes substrate-binding sites and efflux modulation mechanisms within P-glycoprotein. J Chem Inf Model 53(7):1747–1760. doi:10.1021/ci400195v

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Manidhar DM, Kesharwani RK, Reddy NB, Reddy CS, Misra K (2012) Designing, synthesis, and characterization of some novel coumarin derivatives as probable anticancer drugs. Med Chem Res 22:4146–4157

    Article  Google Scholar 

  52. 52.

    Rothnie A, Storm J, McMahon R, Taylor A, Kerr ID, Callaghan R (2005) The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment. FEBS Lett 579(18):3984–3990

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    Raad I, Terreux R, Richomme P, Matera EL, Dumontet C, Raynaud J, Guilet D (2006) Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein. Bioorg Med Chem 14(20):6979–6987

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Kumar S, Mukherjee MM, Varela MF (2013) Modulation of bacterial multidrug resistance efflux pumps of the major facilitator superfamily. Int J Bacteriol 2013:1–15

    Article  Google Scholar 

  55. 55.

    Xu D, Tian W, Shen H (2013) P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent. Mol Med Rep 7(1):115–121. doi:10.3892/mmr.2012.1106

    CAS  PubMed  Google Scholar 

  56. 56.

    Neerati P, Sudhakar YA, Kanwar JR (2013) Curcumin regulates colon cancer by inhibiting P-glycoprotein in in-situ cancerous colon perfusion rat model. J Cancer Sci Ther 5(9):313–319

    PubMed Central  PubMed  Google Scholar 

  57. 57.

    Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB (2008) Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem Pharmacol 76(11):1590–1611. doi:10.1016/j.bcp.2008.08.008

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Vajpeyi R, Misra K (1981) Chemical constituents of Prospis juliflora. Indian J Chem 20(4):348–350

    Google Scholar 

  59. 59.

    Vajpeyi R, Misra K (1981) Two flavonoid glycosides from the bark of Prosopis juliflora. Phytochemistry 20:339–340

    Article  CAS  Google Scholar 

  60. 60.

    Wong IL, Chan KF, Burkett BA, Zhao Y, Chai Y, Sun H, Chan TH, Chow LM (2007) Flavonoid dimers as bivalent modulators for pentamidine and sodium stiboglucanate resistance in leishmania. Antimicrob Agents Chemother 51(3):930–940

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. 61.

    Arora N, Sahi S, Singh N (2013) Structural mapping of inhibitors binding sites on P-glycoprotein: mechanism of inhibition of P-glycoprotein by herbal isoflavones. Int J Biochem Res Rev 3(4):421–435

    Article  CAS  Google Scholar 

  62. 62.

    Jara GE, Vera DM, Pierini AB (2013) Binding of modulators to mouse and human multidrug resistance P-glycoprotein. A computational study. J Mol Graph Model 46:10–21. doi:10.1016/j.jmgm.2013.09.001

    Article  CAS  PubMed  Google Scholar 

  63. 63.

    Zinzi L, Capparelli E, Contino M, Leopoldo M, Colabufo NA (2014) Small and innovative molecules as new strategy to revert MDR. Front Pharmacol 4:2

    Google Scholar 

  64. 64.

    Zaja R, Terzić S, Senta I, Lončar J, Popović M, Ahel M, Smital T (2013) Identification of P-glycoprotein inhibitors in contaminated freshwater sediments. Environ Sci Technol 47(9):4813–4821. doi:10.1021/es400334t

    Article  CAS  PubMed  Google Scholar 

  65. 65.

    Brack W (2003) Effect-directed analysis: a promising tool for the identification of organic toxicants in complex mixtures? Anal Bioanal Chem 377(3):397–407

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Li W, Li X, Gao Y, Zhou Y, Ma S, Zhao Y, Li J, Liu Y, Wang X, Yin D (2014) Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity. Mol Pharm 11(1):71–80. doi:10.1021/mp4004223.-&gt

    Article  CAS  PubMed  Google Scholar 

  67. 67.

    Vilas-Boas V, Silva R, Palmeira A, Sousa E, Ferreira LM, Branco PS, Carvalho F, Bastos Mde L, Remião F (2013) Development of novel rifampicin-derived P-glycoprotein activators/inducers synthesis, in silico analysis and application in the RBE4 cell model, using paraquat as substrate. PLoS One 8(8):e74425. doi:10.1371/journal.pone.0074425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. 68.

    Parveen Z, Stockner T, Bentele C, Pferschy S, Kraupp M, Freissmuth M, Ecker GF, Chiba P (2011) Molecular dissection of dual pseudosymmetric solute translocation pathways in human P-glycoprotein. Mol Pharmacol 79(3):443–452. doi:10.1124/mol.110.067611

    Article  CAS  PubMed  Google Scholar 

  69. 69.

    Qian F, Wei D, Liu J, Yang S (2006) Molecular model and ATPase activity of carboxyl-terminal nucleotide binding domain from human P-glycoprotein. Biochemistry (Mosc). 71(Suppl 1):S18–24, 1–2

  70. 70.

    Di Pietro A, Dayan G, Conseil G, Steinfels E, Krell T, Trompier D, Baubichon-Cortay H, Jault J (1999) P-glycoprotein-mediated resistance to chemotherapy in cancer cells: using recombinant cytosolic domains to establish structure-function relationships. Braz J Med Biol Res 32:925–939

    Article  PubMed  Google Scholar 

  71. 71.

    Conseil G, Baubichon-Cortay H, Dayan G, Jault JM, Barron D, Di Pietro A (1998) Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 95(17):9831–9836

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. 72.

    Leslie EM, Mao Q, Oleschuk CJ, Deeley RG, Cole SP (2001) Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and ATPase activities by interaction with dietary flavonoids. Mol Pharmacol 59(5):1171–1180

    CAS  PubMed  Google Scholar 

  73. 73.

    Kumar A, Khan IA, Koul S, Koul JL, Taneja SC, Ali I, Ali F, Sharma S, Mirza ZM, Kumar M, Sangwan PL, Gupta P, Thota N, Qazi GN (2008) Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J Antimicrob Chemother 61(6):1270–1276. doi:10.1093/jac/dkn088

    Article  CAS  PubMed  Google Scholar 

  74. 74.

    Singh DV, Misra K (ICBF 2008) Bioavailability of Curcumin in the presence of piperine a plausible explanation. International congress on bioprocesses in food industries, Osmania University, Hyderabad, India

  75. 75.

    Singh DV, Godbole MM, Misra K (2011) Role of piperine in enhancing bioavailability of P-gp substrate simulation for next generation of P-gp modulators. World congress on biotechnology Hyderabad, India

  76. 76.

    Tripathi A, Misra K, Kesharwani RK, Singh DV (ICMPB 2012) Study of the role of piperine as inhibitor of drug-efflux using molecular docking, dynamics and QSAR approach. International conference on mycology and plant pathology biotechnological approaches. Banaras Hindu University, Varanasi, India

  77. 77.

    Illmer T, Schaich M, Platzbecker U, Freiberg-Richter J, Oelschlägel U, von Bonin M, Pursche S, Bergemann T, Ehninger G, Schleyer E (2004) P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 18:401–408

    Article  CAS  PubMed  Google Scholar 

  78. 78.

    Lou KJ (2012) Slipping past P glycoprotein. SciBX. 5(39):2012. doi:10.1038/scibx.2012.1019 (Published on line Oct 4

    Google Scholar 

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One of the authors (A. T.) is thankful to Director, Indian Institute of Information Technology, Allahabad for providing necessary facilities and Ministry of Human Resource Development (MHRD) for financial support. (R. K. K.) acknowledges the Indian Council of Medical Research (ICMR), New Delhi, India for providing financial support as Senior Research Fellowship (SRF) that was needed for completing the work. The authors report no conflict of interest.

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Correspondence to Krishna Misra.

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Tripathi, A., Singh, D.V., Kesharwani, R.K. et al. P-Glycoprotein: A Critical Comparison of Models Depicting Mechanism of Drug Efflux and Role of Modulators. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 85, 359–375 (2015).

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  • ATPase activity
  • Efflux mechanism
  • Modulators
  • Nucleotide binding domain
  • P-gp
  • Transmembrane domain