Molecular docking characterizes substrate-binding sites and efflux modulation mechanisms within P-glycoprotein.

Journal of Chemical Information and Modeling

Volumn 53, Issue 7, 2013, Pages 1747-1760

  Ferreira, Ricardo J ^a   Ferreira, Maria José U ^a   Dos Santos, Daniel J V A ^a,b  

^a RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; GLYCOPROTEINS; LIPID BILAYERS; MODULATORS; MOLECULAR MODELING; SUBSTRATES;

CLASSIFICATION MODELS; CONFORMATIONAL CHANGE; CROSS INTERACTIONS; DRUG BINDING SITES; MOLECULAR DOCKING; MULTIDRUG RESISTANCE; REFINED STRUCTURES; SUBSTRATE-BINDING SITES;

BINDING SITES;

DRUG; MULTIDRUG RESISTANCE PROTEIN; PROTEIN BINDING;

ANIMAL; BINDING SITE; CHEMISTRY; HUMAN; METABOLISM; MOLECULAR DOCKING; MOUSE; PROTEIN CONFORMATION; PROTEIN DATABASE; TRANSPORT AT THE CELLULAR LEVEL; ARTICLE; PROTEIN BINDING;

ANIMALS; BINDING SITES; BIOLOGICAL TRANSPORT; DATABASES, PROTEIN; HUMANS; MICE; MOLECULAR DOCKING SIMULATION; P-GLYCOPROTEIN; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; PROTEIN CONFORMATION;

EID: 84880519085     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci400195v     Document Type: Article

References (114)

1. Locher, K. P. Structure and mechanism of ATP-binding cassette transporters Philos. Trans. R. Soc. London, Ser. B 2009, 364, 239-245
2. Tsuruo, T.; Lida, H.; Tsukagoshi, S.; Sakurai, Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil Cancer Res. 1981, 41, 1967-1972
3. Ford, J. M.; Prozialeck, W. C.; Hait, W. N. Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance Mol. Pharmacol. 1989, 35, 105-115
4. Reis, M. A.; Ferreira, R. J.; Santos, M. M. M.; dos Santos, D. J. V. A.; Molnár, J.; Ferreira, M. J. U. Enhancing macrocyclic diterpenes as multidrug-resistance reversers: structure-activity studies on jolkinol D derivatives J. Med. Chem. 2013, 56, 748-760
5. Seelig, A. How does P-glycoprotein recognize its substrates? Int. J. Clin. Pharmacol. Ther. 1998, 36, 50-54
6. Suzuki, T.; Fukazawa, N.; San-nohe, K. Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer J. Med. Chem. 1997, 40, 2047-2052
7. Pearce, H. L.; Safa, A. R.; Bach, N. J.; Winter, M. A.; Cirtain, M. C.; Beck, W. T. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance Proc. Natl. Acad. Sci. U. S. A. 1989, 86, 5128-5132
8. Ferreira, R. J.; dos Santos, D. J. V. A.; Ferreira, M.-J. U.; Guedes, R. C. Toward a better pharmacophore description of P-glycoprotein modulators, based on macrocyclic diterpenes from Euphorbia species J. Chem. Inf. Model. 2011, 51, 1315-1324
9. Pajeva, I. K.; Wiese, M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis) J. Med. Chem. 2002, 45, 5671-5686
10. Pajeva, I. K.; Globisch, C.; Wiese, M. Combined pharmacophore modeling, docking, and 3D QSAR studies of ABCB1 and ABCC1 transporter inhibitors ChemMedChem 2009, 4, 1883-1896
11. Higgins, C. F.; Gottesman, M. M. Is the multidrug transporter a flippase? Trends Biochem. Sci. 1992, 17, 18-21
12. Altenberg, G. A.; Vanoye, C. G.; Horton, J. K.; Reuss, L.; Julie, K. Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: evidence against direct drug extrusion from the plasma membrane Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 4654-4657
13. Raviv, Y.; Pollard, H. B.; Bruggemann, E. P.; Pastan, I.; Gottesman, M. M. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells J. Biol. Chem. 1990, 265, 3975-3980
14. Shapiro, A. B.; Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities Eur. J. Biochem. 1997, 250, 130-137
15. Shapiro, A. B.; Ling, V. Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the rhodamine-123-selective site of P-glycoprotein Eur. J. Biochem. 1998, 254, 181-188
16. Parveen, Z.; Stockner, T.; Bentele, C.; Pferschy, S.; Kraupp, M.; Freissmuth, M.; Ecker, G. F.; Chiba, P. Molecular dissection of dual pseudosymmetric solute translocation pathways in human P-glycoprotein Mol. Pharmacol. 2011, 79, 443-452
17. Pleban, K.; Kopp, S.; Csaszar, E.; Peer, M.; Hrebicek, T.; Rizzi, A.; Ecker, G. F.; Chiba, P. P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach Mol. Pharmacol. 2005, 67, 365-374
18. Loo, T. W.; Clarke, D. M. Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux J. Membr. Biol. 2005, 206, 173-185
19. Shapiro, A. B.; Fox, K.; Lam, P.; Ling, V. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone Eur. J. Biochem. 2001, 259, 841-850
20. Sharom, F. J.; Lugo, M. R.; Eckford, P. D. W. New insights into the drug binding, transport and lipid flippase activities of the p-glycoprotein multidrug transporter J. Bioenerg. Biomembr. 2005, 37, 481-487
21. Lugo, M. R.; Sharom, F. J. Interaction of LDS-751 with P-glycoprotein and mapping of the location of the R drug binding site Biochemistry 2005, 44, 643-655
22. Loo, T. W.; Bartlett, M. C.; Clarke, D. M. Simultaneous binding of two different drugs in the binding pocket of the human multidrug resistance P-glycoprotein J. Biol. Chem. 2003, 278, 39706-39710
23. Loo, T. W.; Clarke, D. M. Do drug substrates enter the common drug-binding pocket of P-glycoprotein through "gates"? Biochem. Biophys. Res. Commun. 2005, 329, 419-422
24. Loo, T. W.; Clarke, D. M. Determining the dimensions of the drug-binding domain of human P-glycoprotein using thiol cross-linking compounds as molecular rulers J. Biol. Chem. 2001, 276, 36877-36880
25. Mandal, D.; Moitra, K.; Ghosh, D.; Xia, D.; Dey, S. Evidence for modulatory sites at the lipid-protein interface of the human multidrug transporter p-glycoprotein Biochemistry 2012, 51, 2852-2866
26. Rosenberg, M. F.; Callaghan, R.; Modok, S.; Higgins, C. F.; Ford, R. C. Three-dimensional structure of P-glycoprotein: the transmembrane regions adopt an asymmetric configuration in the nucleotide-bound state J. Biol. Chem. 2005, 280, 2857-2862
27. Chang, G.; Roth, C. B. Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters Science 2001, 293, 1793-1800
28. Locher, K. P.; Lee, A. T.; Rees, D. C. The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism Science 2002, 296, 1091-1098
29. Loo, T. W.; Bartlett, M. C.; Clarke, D. M. Identification of residues in the drug translocation pathway of the human multidrug resistance P-glycoprotein by arginine mutagenesis J. Biol. Chem. 2009, 284, 24074-24087
30. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242
31. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q.; Urbatsch, I. L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding Science 2009, 323, 1718-1722
32. Jabeen, I.; Wetwitayaklung, P.; Klepsch, F.; Parveen, Z.; Chiba, P.; Ecker, G. F. Probing the stereoselectivity of P-glycoprotein-synthesis, biological activity and ligand docking studies of a set of enantiopure benzopyrano[3,4-b][1,4]oxazines Chem. Commun. (Cambridge, U. K.) 2011, 47, 2586-2588
33. Ford, J. M.; Yang, J. M.; Hait, W. N. P-glycoprotein-mediated multidrug resistance: experimental and clinical strategies for its reversal Cancer Treat. Res. 1996, 87, 3-38
34. Kwon, Y.; Kamath, A. V.; Morris, M. E. Inhibitors of P-glycoprotein- mediated daunomycin transport in rat liver canalicular membrane vesicles J. Pharm. Sci. 1996, 85, 935-939
35. Pajeva, I. K.; Globisch, C.; Wiese, M. Structure-function relationships of multidrug resistance P-glycoprotein J. Biol. Chem. 2004, 47, 2523-2533
36. Dolghih, E.; Bryant, C.; Renslo, A. R.; Jacobson, M. P. Predicting binding to P-glycoprotein by flexible receptor docking PLoS Comput. Biol. 2011, 7, e1002083
37. Hrycyna, C. A.; Airan, L. E.; Germann, U. A.; Ambudkar, S. V; Pastan, I.; Gottesman, M. M. Structural flexibility of the linker region of human P-glycoprotein permits ATP hydrolysis and drug transport Biochemistry 1998, 37, 13660-13673
38. Sato, T.; Kodan, A.; Kimura, Y.; Ueda, K.; Nakatsu, T.; Kato, H. Functional role of the linker region in purified human P-glycoprotein FEBS J. 2009, 276, 3504-3516
39. Ferreira, R. J.; Ferreira, M.-J. U.; dos Santos, D. J. V. A. Assessing the stabilization of P-glycoprotein's nucleotide-binding domains by the linker, using molecular dynamics Mol. Inf. 2013, 32, 529-540
40. Ferreira, R. J.; Ferreira, M. J. U.; dos Santos, D. J. V. A. Insights on P-glycoprotein's efflux mechanism obtained by molecular dynamics simulations J. Chem. Theory Comput. 2012, 8, 1853-1864
41. Jin, M. S.; Oldham, M. L.; Zhang, Q.; Chen, J. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans Nature 2012, 490, 566-569
42. Polli, J. W.; Wring, S. A.; Humphreys, J. E.; Huang, L.; Morgan, J. B.; Webster, L. O.; Serabjit-Singh, C. S. Rational use of in vitro P-glycoprotein assays in drug discovery J. Pharmacol. Exp. Ther. 2001, 299, 620-8
43. Rautio, J.; Humphreys, J. E.; Webster, L. O.; Balakrishnan, A.; Keogh, J. P.; Kunta, J. R.; Serabjit-Singh, C. J.; Polli, J. W. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates Drug Metab. Dispos. 2006, 34, 786-792
44. MarvinSketch 5.11.1, 2012, ChemAxon. http://www.chemaxon.com (accessed June 27, 2013).
45. Molecular Operating Environment (MOE), 2010.10; Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2010.
46. Sanner, M. F. Python: a programming language for software integration and development J. Mol. Graphics Modell. 1999, 17, 57-61
47. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility J. Comput. Chem. 2009, 30, 2785-2791
48. Trott, O.; Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading J. Comput. Chem. 2010, 31, 455-461
49. Brady, G. P.; Stouten, P. F. Fast prediction and visualization of protein binding pockets with PASS J. Comput.-Aided Mol. Des. 2000, 14, 383-401
50. Kohlbacher, O.; Lenhof, H. P. BALL - rapid software prototyping in computational molecular biology. Biochemicals Algorithms Library Bioinformatics 2000, 16, 815-824
51. Eyrisch, S.; Helms, V. Transient pockets on protein surfaces involved in protein-protein interaction J. Med. Chem. 2007, 50, 3457-64
52. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions Protein Eng. 1995, 8, 127-134
53. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins J. Mol. Biol. 1994, 238, 777-793
54. Wang, R. B.; Kuo, C. L.; Lien, L. L.; Lien, E. J.-C. Structure-activity relationship: analyses of p-glycoprotein substrates and inhibitors J. Clin. Pharm. Ther. 2003, 28, 203-228
55. Xue, Y.; Yap, C. W.; Sun, L. Z.; Cao, Z. W.; Wang, J. F.; Chen, Y. Z. Prediction of P-glycoprotein substrates by a support vector machine approach J. Chem. Inf. Comput. Sci. 2004, 44, 1497-1505
56. Cabrera, M. A.; González, I.; Fernández, C.; Navarro, C.; Bermejo, M. A topological substructural approach for the prediction of P-glycoprotein substrates J. Pharm. Sci. 2006, 95, 589-606
57. Wiese, M.; Pajeva, I. K. Structure-activity relationships of multidrug resistance reversers Curr. Med. Chem. 2001, 8, 685-713
58. Loo, T. W.; Clarke, D. M. Identification of residues in the drug-binding domain of human P-glycoprotein. Analysis of transmembrane segment 11 by cysteine-scanning mutagenesis and inhibition by dibromobimane J. Biol. Chem. 1999, 274, 35388-35392
59. Loo, T. W.; Clarke, D. M. Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil J. Biol. Chem. 2001, 276, 14972-14979
60. Loo, T. W.; Clarke, D. M. Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein J. Biol. Chem. 2002, 277, 44332-44338
61. Qu, Q.; Sharom, F. J. Proximity of bound Hoechst 33342 to the ATPase catalytic sites places the drug binding site of P-glycoprotein within the cytoplasmic membrane leaflet Biochemistry 2002, 41, 4744-4752
62. Loo, T. W.; Clarke, D. M. Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane J. Biol. Chem. 2000, 275, 39272-39278
63. Loo, T. W. Identification of residues in the drug-binding site of human P-glycoprotein Using a Thiol-reactive Substrate J. Biol. Chem. 1997, 272, 31945-31948
64. Shapiro, A. B.; Ling, V. Effect of quercetin on Hoechst 33342 transport by purified and reconstituted P-glycoprotein Biochem. Pharmacol. 1997, 53, 587-596
65. Safa, A. R.; Glover, C. J.; Sewell, J. L.; Meyers, M. B.; Biedler, J. L.; Felsted, R. L. Identification of the multidrug resistance-related membrane glycoprotein as an acceptor for calcium channel blockers J. Biol. Chem. 1987, 262, 7884-7888
66. Tamai, I.; Safa, A. R. Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells J. Biol. Chem. 1991, 266, 16796-16800
67. Didziapetris, R.; Japertas, P.; Avdeef, A.; Petrauskas, A. Classification analysis of P-glycoprotein substrate specificity J. Drug Targeting 2003, 11, 391-406
68. Senior, A. E.; Al-Shawi, M. K.; Urbatsch, I. L. The catalytic cycle of P-glycoprotein FEBS Lett. 1995, 377, 285-289
69. Martin, C.; Berridge, G.; Mistry, P.; Higgins, C.; Charlton, P.; Callaghan, R. Drug binding sites on P-glycoprotein are altered by ATP binding prior to nucleotide hydrolysis Biochemistry 2000, 39, 11901-11906
70. Callaghan, R.; Ford, R. C.; Kerr, I. D. The translocation mechanism of P-glycoprotein FEBS Lett. 2006, 580, 1056-1063
71. Siarheyeva, A.; Liu, R.; Sharom, F. J. Characterization of an asymmetric occluded state of P-glycoprotein with two bound nucleotides: implications for catalysis J. Biol. Chem. 2010, 285, 7575-7586
72. Reis, M.; Ferreira, R. J.; Serly, J.; Duarte, N.; Madureira, A. M.; dos Santos, D. J. V. A.; Molnar, J.; Ferreira, M.-J. U. Colon adenocarcinoma multidrug resistance reverted by euphorbia diterpenes: structure-activity relationships and pharmacophore modeling Anticancer Agents Med. Chem. 2012, 12, 1015-1024
73. Gutmann, D. A. P.; Ward, A.; Urbatsch, I. L.; Chang, G.; Van Veen, H. W. Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1 Trends Biochem. Sci. 2010, 35, 36-42
74. Wang, E.; Casciano, C. N.; Clement, R. P.; Johnson, W. W. The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein Cancer Res. 2001, 61, 7525-7529
75. Chen, C.; Hanson, E.; Watson, J. W.; Lee, J. S. P-glycoprotein limits the brain penetration of nonsedating but not sedating H1-antagonists Drug Metab. Dispos. 2003, 31, 312-318
76. Romiti, N.; Tramonti, G.; Chieli, E. Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line Toxicol. Appl. Pharmacol. 2002, 183, 83-91
77. Akiyama, S.; Cornwell, M. M.; Kuwano, M.; Pastan, I.; Gottesman, M. M. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog Mol. Pharmacol. 1988, 33, 144-147
78. Vezmar, M.; Georges, E. Direct binding of chloroquine to the multidrug resistance protein (MRP): possible role for MRP in chloroquine drug transport and resistance in tumor cells Biochem. Pharmacol. 1998, 56, 733-742
79. De Graaf, D.; Sharma, R. C.; Mechetner, E. B.; Schimke, R. T.; Roninson, I. B. P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 1238-1242
80. Norris, M. D.; De Graaf, D.; Haber, M.; Kavallaris, M.; Madafiglio, J.; Gilbert, J.; Kwan, E.; Stewart, B. W.; Mechetner, E. B.; Gudkov, A. V; Roninson, I. B. Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate Int. J. Cancer 1996, 65, 613-619
81. Gifford, A. J.; Kavallaris, M.; Madafiglio, J.; Matherly, L. H.; Stewart, B. W.; Haber, M.; Norris, M. D. P-glycoprotein-mediated methotrexate resistance in CCRF-CEM sublines deficient in methotrexate accumulation due to a point mutation in the reduced folate carrier gene Int. J. Cancer 1998, 78, 176-181
82. Riffkin, C. D.; Chung, R.; Wall, D. M.; Zalcberg, J. R.; Cowman, A. F.; Foley, M.; Tilley, L. Modulation of the function of human MDR1 P-glycoprotein by the antimalarial drug mefloquine Biochem. Pharmacol. 1996, 52, 1545-1552
83. Pham, Y. T.; Régina, A.; Farinotti, R.; Couraud, P.; Wainer, I. W.; Roux, F.; Gimenez, F. Interactions of racemic mefloquine and its enantiomers with P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT Biochim. Biophys. Acta 2000, 1524, 212-219
84. Ford, J. M.; Bruggemann, E. P.; Pastan, I.; Gottesman, M. M.; Hait, W. N. Cellular and biochemical characterization of thioxanthenes for reversal of multidrug resistance in human and murine cell lines Cancer Res. 1990, 50, 1748-1756
85. Ekins, S.; Kim, R. B.; Leake, B. F.; Dantzig, A. H.; Schuetz, E. G.; Lan, L.-B.; Yasuda, K.; Shepard, R. L.; Winter, M. A.; Schuetz, J. D.; Wikel, J. H.; Wrighton, S. A. Application of three-dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates Mol. Pharmacol. 2002, 61, 974-981
86. Ekins, S.; Kim, R. B.; Leake, B. F.; Dantzig, A. H.; Schuetz, E. G.; Lan, L.-B.; Yasuda, K.; Shepard, R. L.; Winter, M. A.; Schuetz, J. D.; Wikel, J. H.; Wrighton, S. A. Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein Mol. Pharmacol. 2002, 61, 964-973
87. Melchior, D. L.; Sharom, F. J.; Evers, R.; Wright, G. E.; Chu, J. W. K.; Wright, S. E.; Chu, X.; Yabut, J. Determining P-glycoprotein-drug interactions: evaluation of reconstituted P-glycoprotein in a liposomal system and LLC-MDR1 polarized cell monolayers J. Pharmacol. Toxicol. Methods 2012, 65, 64-74
88. Wang, E. J.; Lew, K.; Casciano, C. N.; Clement, R. P.; Johnson, W. W. Interaction of common azole antifungals with P glycoprotein Antimicrob. Agents Chemother. 2002, 46, 160-165
89. Kurosawa, M.; Okabe, M.; Hara, N.; Kawamura, K.; Suzuki, S.; Sakurada, K.; Asaka, M. Reversal effect of itraconazole on adriamycin and etoposide resistance in human leukemia cells Ann. Hematol. 1996, 72, 17-21
90. Van Zuylen, L.; Sparreboom, A.; Van der Gaast, A.; Van der Burg, M. E.; Van Beurden, V.; Bol, C. J.; Woestenborghs, R.; Palmer, P. A.; Verweij, J. The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel Clin. Cancer Res. 2000, 6, 1365-1371
91. Van Zuylen, L.; Sparreboom, A.; Van der Gaast, A.; Nooter, K.; Eskens, F. A. L. M.; Brouwer, E.; Bol, C. J.; De Vries, R.; Palmer, P. A.; Verweij, J. Disposition of docetaxel in the presence of P-glycoprotein inhibition by intravenous administration of R101933 Eur. J. Cancer 2002, 38, 1090-1099
92. Duarte, N.; Varga, A.; Cherepnev, G.; Radics, R.; Molnár, J.; Ferreira, M.-J. U. Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids Bioorg. Med. Chem. 2007, 15, 546-554
93. Dantzig, A. H.; Shepard, R. L.; Cao, J.; Law, K. L.; Ehlhardt, W. J.; Baughman, T. M.; Bumol, T. F.; Starling, J. J. Reversal of P-glycoprotein- mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979 Cancer Res. 1996, 56, 4171-4179
94. Kondratov, R. V; Komarov, P. G.; Becker, Y.; Ewenson, A.; Gudkov, A. V Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of P-glycoprotein Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 14078-14083
95. Störmer, E.; Perloff, M. D.; Von Moltke, L. L.; Greenblatt, D. J. Methadone inhibits rhodamine123 transport in Caco-2 cells Drug Metab. Dispos. 2001, 29, 954-956
96. Brooks, T. A.; Minderman, H.; O'Loughlin, K. L.; Pera, P.; Ojima, I.; Baer, M. R.; Bernacki, R. J.; Brooks, T. Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein Mol. Cancer Ther. 2003, 2, 1195-205
97. Storch, C. H.; Theile, D.; Lindenmaier, H.; Haefeli, W. E.; Weiss, J. Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein Biochem. Pharmacol. 2007, 73, 1573-1581
98. Zha, W.; Wang, G.; Xu, W.; Liu, X.; Wang, Y.; Zha, B. S.; Shi, J.; Zhao, Q.; Gerk, P. M.; Studer, E.; Hylemon, P. B.; Pandak, W. M.; Zhou, H. Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages PloS One 2013, 8, e54349
99. Mistry, P.; Stewart, A. J.; Dangerfield, W.; Okiji, S.; Liddle, C.; Bootle, D.; Plumb, J. A.; Templeton, D.; Charlton, P. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576 Cancer Res. 2001, 61, 749-758
100. Sterz, K.; Möllmann, L.; Jacobs, A.; Baumert, D.; Wiese, M. Activators of P-glycoprotein: structure-activity relationships and investigation of their mode of action ChemMedChem 2009, 4, 1897-1911
101. Gozalpour, E.; Wittgen, H. G. M.; Van den Heuvel, J. J. M. W.; Greupink, R.; Russel, F. G. M.; Koenderink, J. B. Interaction of digitalis-like compounds with p-glycoprotein Toxicol. Sci. 2013, 131, 502-511
102. Funakoshi, S.; Murakami, T.; Yumoto, R.; Kiribayashi, Y.; Takano, M. Role of P-glycoprotein in pharmacokinetics and drug interactions of digoxin and beta-methyldigoxin in rats J. Pharm. Sci. 2003, 92, 1455-1463
103. Rebbeor, J. F.; Senior, A. E. Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form Biochim. Biophys. Acta 1998, 1369, 85-93
104. Gannon, M. K.; Holt, J. J.; Bennett, S. M.; Wetzel, B. R.; Loo, T. W.; Bartlett, M. C.; Clarke, D. M.; Sawada, G. A.; Higgins, J. W.; Tombline, G.; Raub, T. J.; Detty, M. R. Rhodamine inhibitors of P-glycoprotein: an amide/thioamide "switch" for ATPase activity J. Med. Chem. 2009, 52, 3328-3341
105. Tenopoulou, M.; Kurz, T.; Doulias, P.-T.; Galaris, D.; Brunk, U. T. Does the calcein-AM method assay the total cellular "labile iron pool" or only a fraction of it? Biochem. J. 2007, 403, 261-266
106. Eckford, P. D. W.; Sharom, F. J. The reconstituted P-glycoprotein multidrug transporter is a flippase for glucosylceramide and other simple glycosphingolipids Biochem. J. 2005, 389, 517-526
107. Garrigues, A.; Escargueil, A. E.; Orlowski, S. The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 10347-10352
108. Lee, A. G. Lipid-protein interactions in biological membranes: a structural perspective Biochim. Biophys. Acta 2003, 1612, 1-40
109. Klappe, K.; Hummel, I.; Hoekstra, D.; Kok, J. W. Lipid dependence of ABC transporter localization and function Chem. Phys. Lipids 2009, 161, 57-64
110. Eytan, G. D.; Regev, R.; Oren, G.; Assaraf, Y. G. The role of passive transbilayer drug movement in multidrug resistance and its modulation J. Biol. Chem. 1996, 271, 12897-12902
111. Urbatsch, I. L.; Senior, A. E. Effects of lipids on ATPase activity of purified Chinese hamster P-glycoprotein Arch. Biochem. Biophys. 1995, 316, 135-40
112. Orlowski, S.; Martin, S.; Escargueil, A. P-glycoprotein and "lipid rafts": some ambiguous mutual relationships (floating on them, building them or meeting them by chance?) Cell. Mol. Life Sci. 2006, 63, 1038-1059
113. Eytan, G. D.; Kuchel, P. W. Mechanism of action of P-glycoprotein in relation to passive membrane permeation Int. Rev. Cytol. 1999, 190, 175-250
114. Regev, R.; Katzir, H.; Yeheskely-Hayon, D.; Eytan, G. D. Modulation of P-glycoprotein-mediated multidrug resistance by acceleration of passive drug permeation across the plasma membrane FEBS Lett. 2007, 274, 6204-6214