Interaction of ABC multidrug transporters with anticancer protein kinase inhibitors: Substrates and/or inhibitors?

Current Cancer Drug Targets

Volumn 9, Issue 3, 2009, Pages 252-272

  Hegedus, Csilla ^a   Özvegy Laczka, Csilla ^a   Szakács, Gergely ^b   Sarkadi, Balázs ^a  

^a SEMMELWEIS UNIVERSITY   (Hungary)

^b INSTITUTE OF ENZYMOLOGY   (Hungary)

Author keywords

ABCG2; MDR ABC transporters; MDR1 Pgp; MRP1; Multidrug resistance; Receptor tyrosine kinases; Small molecule protein kinase inhibitors; Tyrosine kinases

Indexed keywords

2 [2 METHOXY 5 (2,4,6 TRIMETHOXYSTYRYLSULFONYLMETHYL)ANILINO]PROPIONIC ACID; 2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 4 (3 DIMETHYLAMINO 1 PYRROLIDINYLMETHYL) 3 TRIFLUOROMETHYL N [4 METHYL 3 [[4 (5 PYRIMIDINYL) 2 PYRIMIDINYL]AMINO]PHENYL]BENZAMIDE; 4 [3 CHLORO 4 (2 PYRIDINYLMETHOXY)ANILINO] 3 CYANO 6 (4 DIMETHYLAMINOCROTONAMIDO) 7 ETHOXYQUINOLINE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ABC TRANSPORTER; BIBF 1120; BOSUTINIB; CANERTINIB; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; DASATINIB; ERLOTINIB; GEFITINIB; IMATINIB; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MONOCLONAL ANTIBODY; N (5 CHLORO 1,3 BENZODIOXOL 4 YL) 7 [2 (4 METHYL 1 PIPERAZINYL)ETHOXY] 5 (TETRAHYDRO 2H PYRAN 4 YLOXY) 4 QUINAZOLINAMINE; NILOTINIB; PELITINIB; PF 00299804; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; SEMAXANIB; SORAFENIB; SUNITINIB; TEMSIROLIMUS; UNCLASSIFIED DRUG; VANDETANIB; VATALANIB;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; COLORECTAL CARCINOMA; DIGESTIVE SYSTEM CANCER; DRUG EFFECT; DRUG EFFICACY; DRUG METABOLISM; DRUG TARGETING; GASTROINTESTINAL STROMAL TUMOR; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG CANCER; LUNG NON SMALL CELL CANCER; METASTASIS; NEOPLASM; PAIN; PANCREAS CANCER; REVIEW; SOLID TUMOR; TREATMENT RESPONSE; TUMOR CELL; UNSPECIFIED SIDE EFFECT;

ANTINEOPLASTIC AGENTS; APOPTOSIS; ATP-BINDING CASSETTE TRANSPORTERS; CELL DIVISION; CELL SURVIVAL; CLINICAL TRIALS AS TOPIC; DNA DAMAGE; DRUG DESIGN; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES;

EID: 65649147504     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800909788166565     Document Type: Review

References (135)

1. Szakacs, G.; Varadi, A.; Ozvegy-Laczka, C.; Sarkadi, B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov. Today 2008, 13, 379-393.
2. Sarkadi, B.; Homolya, L.; Szakacs, G.; Varadi, A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol. Rev. 2006, 86, 1179-1236. (Pubitemid 44521651)
3. Ishikawa, T. The ATP-dependent glutathione S-conjugate export pump. Trends Biochem. Sci. 1992, 17, 463-468.
4. Klein, S.; McCormick, F.; Levitzki, A. Killing time for cancer cells. Nat. Rev. Cancer 2005, 5, 573-580. (Pubitemid 40942833)
5. Sebolt-Leopold, J. S.; English, J. M. Mechanisms of drug inhibition of signalling molecules. Nature 2006, 441, 457-462. (Pubitemid 44050141)
6. Sawyers, C. Targeted cancer therapy. Nature 2004, 432, 294-297. (Pubitemid 39551656)
7. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science 2002, 298, 1912-1934. (Pubitemid 35425239)
8. Robinson, D. R.; Wu, Y. M.; Lin, S. F. The protein tyrosine kinase family of the human genome. Oncogene 2000, 19, 5548-5557.
9. Blume-Jensen, P.; Hunter, T. Oncogenic kinase signalling. Nature 2001, 411, 355-365. (Pubitemid 32467045)
10. Arslan, M. A.; Kutuk, O.; Basaga, H. Protein kinases as drug targets in cancer. Curr. Cancer Drug Targets 2006, 6, 623-634.
11. Gschwind, A.; Fischer, O. M.; Ullrich, A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat. Rev. Cancer 2004, 4, 361-370. (Pubitemid 38579482)
12. Hubbard, S. R.; Miller, W. T. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr. Opin. Cell Biol. 2007, 19, 117-123. (Pubitemid 46386407)
13. Hynes, N. E.; Lane, H. A. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer 2005, 5, 341-354. (Pubitemid 40637826)
14. Zhang, H.; Berezov, A.; Wang, Q.; Zhang, G.; Drebin, J.; Murali, R.; Greene, M. I. ErbB receptors: from oncogenes to targeted cancer therapies. J. Clin. Invest. 2007, 117, 2051-2058. (Pubitemid 47224766)
15. Ho, Q. T.; Kuo, C. J. Vascular endothelial growth factor: biology and therapeutic applications. Int. J. Biochem. Cell Biol. 2007, 39, 1349-1357. (Pubitemid 47031045)
16. Roskoski, R., Jr. Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit. Rev. Oncol. Hematol. 2007, 62, 179-213. (Pubitemid 46679285)
17. Patnaik, M. M.; Tefferi, A.; Pardanani, A. Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders. Curr. Cancer Drug Targets 2007, 7, 492-503. (Pubitemid 47196209)
18. Lennartsson, J.; Ronnstrand, L. The stem cell factor receptor/c-Kit as a drug target in cancer. Curr. Cancer Drug Targets 2006, 6, 65-75.
19. Ma, P. C.; Kijima, T.; Maulik, G.; Fox, E. A.; Sattler, M.; Griffin, J. D.; Johnson, B. E.; Salgia, R. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 2003, 63, 6272-6281. (Pubitemid 37255174)
20. Markovic, A.; MacKenzie, K. L.; Lock, R. B. FLT-3: a new focus in the understanding of acute leukemia. Int. J. Biochem. Cell Biol. 2005, 37, 1168-1172. (Pubitemid 40381193)
21. Lewis, N. L. The platelet-derived growth factor receptor as a therapeutic target. Curr. Oncol. Rep. 2007, 9, 89-95. (Pubitemid 46332379)
22. Ren, R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukemia. Nat. Rev. Cancer 2005, 5, 172-183. (Pubitemid 40314949)
23. Rao, R. D.; Buckner, J. C.; Sarkaria, J. N. Mammalian target of rapamycin (mTOR) inhibitors as anti-cancer agents. Curr. Cancer Drug Targets 2004, 4, 621-635. (Pubitemid 40013570)
24. Faivre, S.; Kroemer, G.; Raymond, E. Current development of mTOR inhibitors as anticancer agents. Nat. Rev. Drug Discov. 2006, 5, 671-688. (Pubitemid 44151605)
25. Noble, M. E.; Endicott, J. A.; Johnson, L. N. Protein kinase inhibitors: insights into drug design from structure. Science 2004, 303, 1800-1805. (Pubitemid 38374863)
26. Wang, Z.; Canagarajah, B. J.; Boehm, J. C.; Kassisa, S.; Cobb, M. H.; Young, P. R.; Abdel-Meguid, S.; Adams, J. L.; Goldsmith, E. J. Structural basis of inhibitor selectivity in MAP kinases. Structure 1998, 6, 1117-1128. (Pubitemid 28434115)
27. Fitzgerald, C. E.; Patel, S. B.; Becker, J. W.; Cameron, P. M.; Zaller, D.; Pikounis, V. B.; O'Keefe, S. J.; Scapin, G. Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity. Nat. Struct. Biol. 2003, 10, 764-769. (Pubitemid 37052417)
28. Bogoyevitch, M. A.; Fairlie, D. P. A new paradigm for protein kinase inhibition: blocking phosphorylation without directly targeting ATP binding. Drug Discov. Today 2007, 12, 622-633. (Pubitemid 47238645)
29. Buchdunger, E.; Zimmermann, J.; Mett, H.; Meyer, T.; Muller, M.; Druker, B. J.; Lydon, N. B. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996, 56, 100-104. (Pubitemid 26011463)
30. Druker, B. J.; Tamura, S.; Buchdunger, E.; Ohno, S.; Segal, G. M.; Fanning, S.; Zimmermann, J.; Lydon, N. B. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 1996, 2, 561-566. (Pubitemid 26151518)
31. Deininger, M. W.; Goldman, J. M.; Lydon, N.; Melo, J. V. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 1997, 90, 3691-3698. (Pubitemid 27473440)
32. Carroll, M.; Ohno-Jones, S.; Tamura, S.; Buchdunger, E.; Zimmermann, J.; Lydon, N. B.; Gilliland, D. G.; Druker, B. J. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 1997, 90, 4947-4952. (Pubitemid 28007210)
33. Gambacorti-Passerini, C.; le Coutre, P.; Mologni, L.; Fanelli, M.; Bertazzoli, C.; Marchesi, E.; Di Nicola, M.; Biondi, A.; Corneo, G. M.; Belotti, D.; Pogliani, E.; Lydon, N. B. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol. Dis. 1997, 23, 380-394.
34. Weisberg, E.; Manley, P. W.; Cowan-Jacob, S. W.; Hochhaus, A.; Griffin, J. D. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukemia. Nat. Rev. Cancer 2007, 7, 345-356. (Pubitemid 46652483)
35. Quintas-Cardama, A.; Kantarjian, H.; Cortes, J. Flying under the radar: the new wave of BCR-ABL inhibitors. Nat. Rev. Drug Discov. 2007, 6, 834-848. (Pubitemid 47500507)
36. Bantscheff, M.; Eberhard, D.; Abraham, Y.; Bastuck, S.; Boesche, M.; Hobson, S.; Mathieson, T.; Perrin, J.; Raida, M.; Rau, C.; Reader, V.; Sweetman, G.; Bauer, A.; Bouwmeester, T.; Hopf, C.; Kruse, U.; Neubauer, G.; Ramsden, N.; Rick, J.; Kuster, B.; Drewes, G. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat. Biotechnol. 2007, 25, 1035-1044. (Pubitemid 47517638)
37. Rix, U.; Hantschel, O.; Durnberger, G.; Remsing Rix, L. L.; Planyavsky, M.; Fernbach, N. V.; Kaupe, I.; Bennett, K. L.; Valent, P.; Colinge, J.; Kocher, T.; Superti-Furga, G. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 2007, 110, 4055-4063. (Pubitemid 350248462)
38. Albanell, J.; Gascon, P. Small molecules with EGFR-TK inhibitor activity. Curr. Drug Targets 2005, 6, 259-274. (Pubitemid 40667794)
39. Sequist, L. V. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Oncologist 2007, 12, 325-330. (Pubitemid 46556799)
40. Sergina, N. V.; Rausch, M.; Wang, D.; Blair, J.; Hann, B.; Shokat, K. M.; Moasser, M. M. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007, 445, 437-441. (Pubitemid 46160912)
41. Engelman, J. A.; Zejnullahu, K.; Gale, C. M.; Lifshits, E.; Gonzales, A. J.; Shimamura, T.; Zhao, F.; Vincent, P. W.; Naumov, G. N.; Bradner, J. E.; Althaus, I. W.; Gandhi, L.; Shapiro, G. I.; Nelson, J. M.; Heymach, J. V.; Meyerson, M.; Wong, K. K.; Janne, P. A. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007, 67, 11924-11932.
42. Schenone, S.; Bondavalli, F.; Botta, M. Antiangiogenic agents: an update on small molecule VEGFR inhibitors. Curr. Med. Chem. 2007, 14, 2495-2516. (Pubitemid 47618038)
43. Sabatini, D. M. mTOR and cancer: insights into a complex relationship. Nat. Rev. Cancer 2006, 6, 729-734. (Pubitemid 44286004)
44. Dawson, R. J.; Locher, K. P. Structure of a bacterial multidrug ABC transporter. Nature 2006, 443, 180-185. (Pubitemid 44387602)
45. Pastan, I.; Gottesman, M. M. Multidrug resistance. Annu. Rev. Med. 1991, 42, 277-286
46. Allen, J. D.; van Loevezijn, A.; Lakhai, J. M.; van der Valk, M.; van Tellingen, O.; Reid, G.; Schellens, J. H.; Koomen, G. J.; Schinkel, A. H. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol. Cancer Ther. 2002, 1, 417-425.
47. Deeley, R. G.; Westlake, C.; Cole, S. P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev. 2006, 86, 849-899. (Pubitemid 44033384)
48. Bakos, E.; Hegedus, T.; Hollo, Z.; Welker, E.; Tusnady, G. E.; Zaman, G. J.; Flens, M. J.; Varadi, A.; Sarkadi, B. Membrane topology and glycosylation of the human multidrug resistance-associated protein. J. Biol. Chem. 1996, 271, 12322-12326. (Pubitemid 26160897)
49. Bakos, E.; Evers, R.; Szakacs, G.; Tusnady, G. E.; Welker, E.; Szabo, K.; de Haas, M.; van Deemter, L.; Borst, P.; Varadi, A.; Sarkadi, B. Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain. J. Biol. Chem. 1998, 273, 32167-32175. (Pubitemid 29177162)
50. Bakos, E.; Homolya, L. Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1). Pflugers Arch. 2007, 453, 621-641. (Pubitemid 46192535)
51. Szakacs, G.; Paterson, J. K.; Ludwig, J. A.; Booth-Genthe, C.; Gottesman, M. M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 2006, 5, 219-234. (Pubitemid 43336035)
52. Ozvegy, C.; Varadi, A.; Sarkadi, B. Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation. J. Biol. Chem. 2002, 277, 47980-47990. (Pubitemid 35470743)
53. Tanaka, Y.; Slitt, A. L.; Leazer, T. M.; Maher, J. M.; Klaassen, C. D. Tissue distribution and hormonal regulation of the breast cancer resistance protein (Bcrp/Abcg2) in rats and mice. Biochem. Biophys. Res. Commun. 2005, 326, 181-187.
54. Abbott, B. L. ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells. Clin. Adv. Hematol. Oncol. 2006, 4, 63-72. (Pubitemid 43173716)
55. Zhou, S.; Schuetz, J. D.; Bunting, K. D.; Colapietro, A. M.; Sampath, J.; Morris, J. J.; Lagutina, I.; Grosveld, G. C.; Osawa, M.; Nakauchi, H.; Sorrentino, B. P. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 2001, 7, 1028-1034. (Pubitemid 32937383)
56. Kim, M.; Turnquist, H.; Jackson, J.; Sgagias, M.; Yan, Y.; Gong, M.; Dean, M.; Sharp, J. G.; Cowan, K. The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin. Cancer Res. 2002, 8, 22-28. (Pubitemid 34101455)
57. Dean, M.; Fojo, T.; Bates, S. Tumour stem cells and drug resistance. Nat. Rev. Cancer 2005, 5, 275-284. (Pubitemid 40488633)
58. Cervenak, J.; Andrikovics, H.; Ozvegy-Laczka, C.; Tordai, A.; Nemet, K.; Varadi, A.; Sarkadi, B. The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology. Cancer Lett. 2006, 234, 62-72. (Pubitemid 43348491)
59. Lee, S. S.; Jeong, H. E.; Yi, J. M.; Jung, H. J.; Jang, J. E.; Kim, E. Y.; Lee, S. J.; Shin, J. G. Identification and functional assessment of BCRP polymorphisms in a Korean population. Drug Metab. Dispos. 2007, 35, 623-632. (Pubitemid 46513266)
60. de Jong, F. A.; Marsh, S.; Mathijssen, R. H.; King, C.; Verweij, J.; Sparreboom, A.; McLeod, H. L. ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin. Cancer Res. 2004, 10, 5889-5894. (Pubitemid 39180970)
61. Sparreboom, A.; Gelderblom, H.; Marsh, S.; Ahluwalia, R.; Obach, R.; Principe, P.; Twelves, C.; Verweij, J.; McLeod, H. L. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin. Pharmacol. Ther. 2004, 76, 38-44. (Pubitemid 38844732)
62. Zhang, W.; Yu, B. N.; He, Y. J.; Fan, L.; Li, Q.; Liu, Z. Q.; Wang, A.; Liu, Y. L.; Tan, Z. R.; Fen, J.; Huang, Y. F.; Zhou, H. H. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin. Chim. Acta. 2006, 373, 99-103. (Pubitemid 44292182)
63. Ieiri, I.; Suwannakul, S.; Maeda, K.; Uchimaru, H.; Hashimoto, K.; Kimura, M.; Fujino, H.; Hirano, M.; Kusuhara, H.; Irie, S.; Higuchi, S.; Sugiyama, Y. SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers. Clin. Pharmacol. Ther. 2007, 82, 541-547. (Pubitemid 47622520)
64. Ho, R. H.; Choi, L.; Lee, W.; Mayo, G.; Schwarz, U. I.; Tirona, R. G.; Bailey, D. G.; Michael Stein, C.; Kim, R. B. Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants. Pharmacogenet. Genomics 2007, 17, 647-656. (Pubitemid 47057714)
65. Kim, H. S.; Sunwoo, Y. E.; Ryu, J. Y.; Kang, H. J.; Jung, H. E.; Song, I. S.; Kim, E. Y.; Shim, J. C.; Shon, J. H.; Shin, J. G. The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br. J. Clin. Pharmacol. 2007, 64, 645-654. (Pubitemid 47568815)
66. Tamura, A.; Watanabe, M.; Saito, H.; Nakagawa, H.; Kamachi, T.; Okura, I.; Ishikawa, T. Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport. Mol. Pharmacol. 2006, 70, 287-296. (Pubitemid 43920818)
67. Xia, C. Q.; Milton, M. N.; Gan, L. S. Evaluation of drug-transporter interactions using in vitro and in vivo models. Curr. Drug Metab. 2007, 8, 341-363. (Pubitemid 46780063)
68. Varma, M. V.; Ashokraj, Y.; Dey, C. S.; Panchagnula, R. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol. Res. 2003, 48, 347-359. (Pubitemid 36945333)
69. Hollo, Z.; Homolya, L.; Hegedus, T.; Muller, M.; Szakacs, G.; Jakab, K.; Antal, F.; Sarkadi, B. Parallel functional and immunological detection of human multidrug resistance proteins, Pglycoprotein and MRP1. Anticancer Res. 1998, 18, 2981-2987. (Pubitemid 28388802)
70. Mahon, F. X.; Deininger, M. W.; Schultheis, B.; Chabrol, J.; Reiffers, J.; Goldman, J. M.; Melo, J. V. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 2000, 96, 1070-1079. (Pubitemid 30616875)
71. Mahon, F. X.; Belloc, F.; Lagarde, V.; Chollet, C.; Moreau-Gaudry, F.; Reiffers, J.; Goldman, J. M.; Melo, J. V. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 2003, 101, 2368-2373. (Pubitemid 36304670)
72. Hegedus, T.; Orfi, L.; Seprodi, A.; Varadi, A.; Sarkadi, B.; Keri, G. Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1. Biochim. Biophys. Acta. 2002, 1587, 318-325. (Pubitemid 34655800)
73. Hamada, A.; Miyano, H.; Watanabe, H.; Saito, H. Interaction of imatinib mesilate with human P-glycoprotein. J. Pharmacol. Exp. Ther. 2003, 307, 824-828. (Pubitemid 37310701)
74. Kotaki, M.; Motoji, T.; Takanashi, M.; Wang, Y. H.; Mizoguchi, H. Anti-proliferative effect of the abl tyrosine kinase inhibitor STI571 on the P-glycoprotein positive K562/ADM cell line. Cancer Lett. 2003, 199, 61-68. (Pubitemid 37088139)
75. Thomas, J.; Wang, L.; Clark, R. E.; Pirmohamed, M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004, 104, 3739-3745. (Pubitemid 39564452)
76. Theou, N.; Gil, S.; Devocelle, A.; Julie, C.; Lavergne-Slove, A.; Beauchet, A.; Callard, P.; Farinotti, R.; Le Cesne, A.; Lemoine, A.; Faivre-Bonhomme, L.; Emile, J. F. Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent expression and initial response to imatinib. Clin. Cancer Res. 2005, 11, 7593-7598. (Pubitemid 41611598)
77. Zong, Y.; Zhou, S.; Sorrentino, B. P. Loss of P-glycoprotein expression in hematopoietic stem cells does not improve responses to imatinib in a murine model of chronic myelogenous leukemia. Leukemia 2005, 19, 1590-1596. (Pubitemid 43090403)
78. Mukai, M.; Che, X. F.; Furukawa, T.; Sumizawa, T.; Aoki, S.; Ren, X. Q.; Haraguchi, M.; Sugimoto, Y.; Kobayashi, M.; Takamatsu, H.; Akiyama, S. Reversal of the resistance to STI571 in human chronic myelogenous leukemia K562 cells. Cancer Sci. 2003, 94, 557-563. (Pubitemid 36849722)
79. Radujkovic, A.; Schad, M.; Topaly, J.; Veldwijk, M. R.; Laufs, S.; Schultheis, B. S.; Jauch, A.; Melo, J. V.; Fruehauf, S.; Zeller, W. J. Synergistic activity of imatinib and 17-AAG in imatinib-resistant CML cells overexpressing BCR-ABL - Inhibition of P-glycoprotein function by 17-AAG. Leukemia 2005, 19, 1198-1206. (Pubitemid 40946004)
80. Yokota, A.; Kimura, S.; Masuda, S.; Ashihara, E.; Kuroda, J.; Sato, K.; Kamitsuji, Y.; Kawata, E.; Deguchi, Y.; Urasaki, Y.; Terui, Y.; Ruthardt, M.; Ueda, T.; Hatake, K.; Inui, K.; Maekawa, T. INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity. Blood 2007, 109, 306-314. (Pubitemid 46053071)
81. Ozvegy-Laczka, C.; Hegedus, T.; Varady, G.; Ujhelly, O.; Schuetz, J. D.; Varadi, A.; Keri, G.; Orfi, L.; Nemet, K.; Sarkadi, B. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol. Pharmacol. 2004, 65, 1485-1495. (Pubitemid 38668306)
82. Brendel, C.; Scharenberg, C.; Dohse, M.; Robey, R. W.; Bates, S. E.; Shukla, S.; Ambudkar, S. V.; Wang, Y.; Wennemuth, G.; Burchert, A.; Boudriot, U.; Neubauer, A. Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia 2007, 21, 1267-1275. (Pubitemid 46831816)
83. Shukla, S.; Sauna, Z. E.; Ambudkar, S. V. Evidence for the interaction of imatinib at the transport-substrate site(s) of the multidrug-resistance-linked ABC drug transporters ABCB1 (P-glycoprotein) and ABCG2. Leukemia 2007.
84. McDowell, H. P.; Meco, D.; Riccardi, A.; Tanno, B.; Berardi, A. C.; Raschella, G.; Riccardi, R.; Dominici, C. Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models. Int. J. Cancer 2007, 120, 1141-1149. (Pubitemid 46214319)
85. Houghton, P. J.; Germain, G. S.; Harwood, F. C.; Schuetz, J. D.; Stewart, C. F.; Buchdunger, E.; Traxler, P. Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004, 64, 2333-2337. (Pubitemid 38523883)
86. Jordanides, N. E.; Jorgensen, H. G.; Holyoake, T. L.; Mountford, J. C. Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood 2006, 108, 1370-1373. (Pubitemid 44232038)
87. Nakanishi, T.; Shiozawa, K.; Hassel, B. A.; Ross, D. D. Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib-induced reduction of BCRP expression. Blood 2006, 108, 678-684. (Pubitemid 44061370)
88. Burger, H.; van Tol, H.; Boersma, A. W.; Brok, M.; Wiemer, E. A.; Stoter, G.; Nooter, K. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 2004, 104, 2940-2942. (Pubitemid 39434984)
89. Burger, H.; Nooter, K. Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinib. Cell Cycle 2004, 3, 1502-1505. (Pubitemid 40521401)
90. Burger, H.; van Tol, H.; Brok, M.; Wiemer, E. A.; de Bruijn, E. A.; Guetens, G.; de Boeck, G.; Sparreboom, A.; Verweij, J.; Nooter, K. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol. Ther. 2005, 4, 747-752. (Pubitemid 41351174)
91. Jiang, X.; Zhao, Y.; Smith, C.; Gasparetto, M.; Turhan, A.; Eaves, A.; Eaves, C. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia 2007, 21, 926-935. (Pubitemid 46672068)
92. White, D. L.; Saunders, V. A.; Dang, P.; Engler, J.; Zannettino, A. C.; Cambareri, A. C.; Quinn, S. R.; Manley, P. W.; Hughes, T. P. OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 2006, 108, 697-704. (Pubitemid 44061372)
93. White, D. L.; Saunders, V. A.; Quinn, S. R.; Manley, P. W.; Hughes, T. P. Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugs. Blood 2007, 109, 3609-3610. (Pubitemid 46572560)
94. Mahon, F. X.; Hayette, S.; Lagarde, V.; Belloc, F.; Turcq, B.; Nicolini, F.; Belanger, C.; Manley, P. W.; Leroy, C.; Etienne, G.; Roche, S.; Pasquet, J. M. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res. 2008, 68, 9809-9816.
95. Hiwase, D. K.; Saunders, V.; Hewett, D.; Frede, A.; Zrim, S.; Dang, P.; Eadie, L.; To, L. B.; Melo, J.; Kumar, S.; Hughes, T. P.; White, D. L. Dasatinib cellular uptake and efflux in chronic myeloid leukemia cells: therapeutic implications. Clin. Cancer Res. 2008, 14, 3881-3888.
96. Giannoudis, A.; Davies, A.; Lucas, C. M.; Harris, R. J.; Pirmohamed, M.; Clark, R. E. Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood 2008, 112, 3348-3354.
97. Kitazaki, T.; Oka, M.; Nakamura, Y.; Tsurutani, J.; Doi, S.; Yasunaga, M.; Takemura, M.; Yabuuchi, H.; Soda, H.; Kohno, S. Gefitinib, an EGFR tyrosine kinase inhibitor, directly inhibits the function of P-glycoprotein in multidrug resistant cancer cells. Lung Cancer 2005, 49, 337-343. (Pubitemid 41139146)
98. Yang, C. H.; Huang, C. J.; Yang, C. S.; Chu, Y. C.; Cheng, A. L.; Whang-Peng, J.; Yang, P. C. Gefitinib reverses chemotherapy resistance in gefitinib-insensitive multidrug resistant cancer cells expressing ATP-binding cassette family protein. Cancer Res. 2005, 65, 6943-6949. (Pubitemid 41060734)
99. Mi, Y.; Lou, L. ZD6474 reverses multidrug resistance by directly inhibiting the function of P-glycoprotein. Br. J. Cancer 2007, 97, 934-940. (Pubitemid 47519322)
100. Shi, Z.; Peng, X. X.; Kim, I. W.; Shukla, S.; Si, Q. S.; Robey, R. W.; Bates, S. E.; Shen, T.; Ashby, C. R., Jr.; Fu, L. W.; Ambudkar, S. V.; Chen, Z. S. Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance. Cancer Res. 2007, 67, 11012-11020. (Pubitemid 350145931)
101. Marchetti, S.; de Vries, N. A.; Buckle, T.; Bolijn, M. J.; van Eijndhoven, M. A.; Beijnen, J. H.; Mazzanti, R.; van Tellingen, O.; Schellens, J. H. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol. Cancer Ther. 2008, 7, 2280-2287.
102. Klement, G.; Huang, P.; Mayer, B.; Green, S. K.; Man, S.; Bohlen, P.; Hicklin, D.; Kerbel, R. S. Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. Clin. Cancer Res. 2002, 8, 221-232. (Pubitemid 34101482)
103. Busby, J. E.; Kim, S. J.; Yazici, S.; Nakamura, T.; Kim, J. S.; He, J.; Maya, M.; Wang, X.; Do, K. A.; Fan, D.; Fidler, I. J. Therapy of multidrug resistant human prostate tumors in the prostate of nude mice by simultaneous targeting of the epidermal growth factor receptor and vascular endothelial growth factor receptor on tumor-associated endothelial cells. Prostate 2006, 66, 1788-1798.
104. Dai, C. L.; Tiwari, A. K.; Wu, C. P.; Su, X. D.; Wang, S. R.; Liu, D. G.; Ashby, C. R., Jr.; Huang, Y.; Robey, R. W.; Liang, Y. J.; Chen, L. M.; Shi, C. J.; Ambudkar, S. V.; Chen, Z. S.; Fu, L. W. Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Res. 2008, 68, 7905-7914.
105. Polli, J. W.; Humphreys, J. E.; Harmon, K. A.; Castellino, S.; O'Mara, M. J.; Olson, K. L.; John-Williams, L. S.; Koch, K. M.; Serabjit-Singh, C. J. The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy] phenyl}-6-[5-({[2-(methylsulfonyl)ethy l]amino}methyl)-2-furyl]-4- quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab. Dispos. 2008, 36, 695-701.
106. Elkind, N. B.; Szentpetery, Z.; Apati, A.; Ozvegy-Laczka, C.; Varady, G.; Ujhelly, O.; Szabo, K.; Homolya, L.; Varadi, A.; Buday, L.; Keri, G.; Nemet, K.; Sarkadi, B. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). Cancer Res. 2005, 65, 1770-1777. (Pubitemid 40478603)
107. Yanase, K.; Tsukahara, S.; Asada, S.; Ishikawa, E.; Imai, Y.; Sugimoto, Y. Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol. Cancer Ther. 2004, 3, 1119-1125. (Pubitemid 39295009)
108. Liu, H.; Cheng, D.; Weichel, A. K.; Osipo, C.; Wing, L. K.; Chen, B.; Louis, T. E.; Jordan, V. C. Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Int. J. Oncol. 2006, 29, 1237-1246.
109. Stewart, C. F.; Leggas, M.; Schuetz, J. D.; Panetta, J. C.; Cheshire, P. J.; Peterson, J.; Daw, N.; Jenkins, J. J., 3rd; Gilbertson, R.; Germain, G. S.; Harwood, F. C.; Houghton, P. J. Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res. 2004, 64, 7491-7499.
110. Nakamura, Y.; Oka, M.; Soda, H.; Shiozawa, K.; Yoshikawa, M.; Itoh, A.; Ikegami, Y.; Tsurutani, J.; Nakatomi, K.; Kitazaki, T.; Doi, S.; Yoshida, H.; Kohno, S. Gefitinib ("Iressa", ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ABCG2-mediated drug resistance. Cancer Res. 2005, 65, 1541-1546.
111. Li, J.; Cusatis, G.; Brahmer, J.; Sparreboom, A.; Robey, R. W.; Bates, S. E.; Hidalgo, M.; Baker, S. D. Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer Biol. Ther. 2007, 6, 432-438. (Pubitemid 47328313)
112. Leggas, M.; Panetta, J. C.; Zhuang, Y.; Schuetz, J. D.; Johnston, B.; Bai, F.; Sorrentino, B.; Zhou, S.; Houghton, P. J.; Stewart, C. F. Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer Res. 2006, 66, 4802-4807.
113. Lopez, J. P.; Wang-Rodriguez, J.; Chang, C.; Chen, J. S.; Pardo, F. S.; Aguilera, J.; Ongkeko, W. M. Gefitinib inhibition of drug resistance to doxorubicin by inactivating ABCG2 in thyroid cancer cell lines. Arch. Otolaryngol. Head Neck Surg. 2007, 133, 1022-1027. (Pubitemid 47607585)
114. Usuda, J.; Ohira, T.; Suga, Y.; Oikawa, T.; Ichinose, S.; Inoue, T.; Ohtani, K.; Maehara, S.; Imai, K.; Kubota, M.; Tsunoda, Y.; Tsutsui, H.; Furukawa, K.; Okunaka, T.; Sugimoto, Y.; Kato, H. Breast cancer resistance protein (BCRP) affected acquired resistance to gefitinib in a "never-smoked" female patient with advanced non-small cell lung cancer. Lung Cancer 2007, 58, 296-299.
115. Chen, J. S.; Pardo, F. S.; Wang-Rodriguez, J.; Chu, T. S.; Lopez, J. P.; Aguilera, J.; Altuna, X.; Weisman, R. A.; Ongkeko, W. M. EGFR regulates the side population in head and neck squamous cell carcinoma. Laryngoscope 2006, 116, 401-406. (Pubitemid 44318100)
116. Azzariti, A.; Porcelli, L.; Xu, J. M.; Simone, G. M.; Paradiso, A. Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib (Iressa(TM)) and to the antiangiogenic agent ZD6474: Cytotoxic and biomolecular effects. World J. Gastroenterol. 2006, 12, 5140-5147. (Pubitemid 44355909)
117. Polli, J. W.; Olson, K. L.; Chism, J. P.; John-Williams, L. S.; Yeager, R. L.; Woodard, S. M.; Otto, V.; Castellino, S.; Demby, V. E. An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl] amino}methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab. Dispos. 2009, 37, 439-442.
118. Erlichman, C.; Boerner, S. A.; Hallgren, C. G.; Spieker, R.; Wang, X. Y.; James, C. D.; Scheffer, G. L.; Maliepaard, M.; Ross, D. D.; Bible, K. C.; Kaufmann, S. H. The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res. 2001, 61, 739-748. (Pubitemid 32128641)
119. Xiao, Y.; Davidson, R.; Smith, A.; Pereira, D.; Zhao, S.; Soglia, J.; Gebhard, D.; de Morais, S.; Duignan, D. B. A 96-well efflux assay to identify ABCG2 substrates using a stably transfected MDCK II cell line. Mol. Pharm. 2006, 3, 45-54. (Pubitemid 43331750)
120. Shukla, S.; Robey, R. W.; Bates, S. E.; Ambudkar, S. V. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab. Dispos. 2009, 37, 359-365.
121. Paine, M. F.; Leung, L. Y.; Watkins, P. B. New insights into drug absorption: studies with sirolimus. Ther. Drug Monit. 2004, 26, 463-467. (Pubitemid 39314311)
122. Pawarode, A.; Shukla, S.; Minderman, H.; Fricke, S. M.; Pinder, E. M.; O'Loughlin, K. L.; Ambudkar, S. V.; Baer, M. R. Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins. Cancer Chemother. Pharmacol. 2007, 60, 179-188. (Pubitemid 46742532)
123. Gupta, A.; Dai, Y.; Vethanayagam, R. R.; Hebert, M. F.; Thummel, K. E.; Unadkat, J. D.; Ross, D. D.; Mao, Q. Cyclosporin A, tacrolimus and sirolimus are potent inhibitors of the human breast cancer resistance protein (ABCG2) and reverse resistance to mitoxantrone and topotecan. Cancer Chemother. Pharmacol. 2006, 58, 374-383. (Pubitemid 43800742)
124. Cusatis, G.; Gregorc, V.; Li, J.; Spreafico, A.; Ingersoll, R. G.; Verweij, J.; Ludovini, V.; Villa, E.; Hidalgo, M.; Sparreboom, A.; Baker, S. D. Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J. Natl. Cancer Inst. 2006, 98, 1739-1742.
125. Rudin, C. M.; Liu, W.; Desai, A.; Karrison, T.; Jiang, X.; Janisch, L.; Das, S.; Ramirez, J.; Poonkuzhali, B.; Schuetz, E.; Fackenthal, D. L.; Chen, P.; Armstrong, D. K.; Brahmer, J. R.; Fleming, G. F.; Vokes, E. E.; Carducci, M. A.; Ratain, M. J. Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity. J. Clin. Oncol. 2008, 26, 1119-1127.
126. Gardner, E. R.; Burger, H.; van Schaik, R. H.; van Oosterom, A. T.; de Bruijn, E. A.; Guetens, G.; Prenen, H.; de Jong, F. A.; Baker, S. D.; Bates, S. E.; Figg, W. D.; Verweij, J.; Sparreboom, A.; Nooter, K. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin. Pharmacol. Ther. 2006, 80, 192-201. (Pubitemid 44160695)
127. Judson, I.; Ma, P.; Peng, B.; Verweij, J.; Racine, A.; di Paola, E. D.; van Glabbeke, M.; Dimitrijevic, S.; Scurr, M.; Dumez, H.; van Oosterom, A. Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother. Pharmacol. 2005, 55, 379-386. (Pubitemid 40379262)
128. Bihorel, S.; Camenisch, G.; Lemaire, M.; Scherrmann, J. M. Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier. J. Neurochem. 2007, 102, 1749-1757. (Pubitemid 47329285)
129. Bihorel, S.; Camenisch, G.; Lemaire, M.; Scherrmann, J. M. Modulation of the brain distribution of imatinib and its metabolites in mice by valspodar, zosuquidar and elacridar. Pharm. Res. 2007, 24, 1720-1728. (Pubitemid 47206611)
130. Breedveld, P.; Pluim, D.; Cipriani, G.; Wielinga, P.; van Tellingen, O.; Schinkel, A. H.; Schellens, J. H. The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005, 65, 2577-2582. (Pubitemid 40490054)
131. Zhuang, Y.; Fraga, C. H.; Hubbard, K. E.; Hagedorn, N.; Panetta, J. C.; Waters, C. M.; Stewart, C. F. Topotecan central nervous system penetration is altered by a tyrosine kinase inhibitor. Cancer Res. 2006, 66, 11305-11313. (Pubitemid 46009961)
132. Zheleznova, E. E.; Markham, P.; Edgar, R.; Bibi, E.; Neyfakh, A. A.; Brennan, R. G. A structure-based mechanism for drug binding by multidrug transporters. Trends Biochem. Sci. 2000, 25, 39-43. (Pubitemid 30100360)
133. Pajeva, I. K.; Globisch, C.; Wiese, M. Structure-function relationships of multidrug resistance P-glycoprotein. J. Med. Chem. 2004, 47, 2523-2533. (Pubitemid 38580090)
134. Pawagi, A. B.; Wang, J.; Silverman, M.; Reithmeier, R. A.; Deber, C. M. Transmembrane aromatic amino acid distribution in P-glycoprotein. A functional role in broad substrate specificity. J. Mol. Biol. 1994, 235, 554-564. (Pubitemid 124001687)
135. Loo, T. W.; Bartlett, M. C.; Clarke, D. M. Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding. J. Biol. Chem. 2003, 278, 13603-13606. (Pubitemid 36799891)