In silico prediction of substrate properties for ABC-multidrug transporters

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 9, 2008, Pages 1167-1180

  Demel, Michael A ^a   Schwaha, R ^a   Kramer O ^b   Ettmayer, P ^b   Haaksma, Eric E J ^b   Ecker, Gerhard F ^a  

^a UNIVERSITY OF VIENNA   (Austria)

^b BOEHRINGER INGELHEIM RCV GMBH AND CO KG   (Austria)

Author keywords

ABC transporter; ABCB1; Machine learning; P glycoprotein; Pharmacophore modelling; Substrate; Support vector machine

Indexed keywords

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATASE; BREAST CANCER RESISTANCE PROTEIN; BREAST CANCER RESISTANCE PROTEIN INHIBITOR; CYCLOSPORIN; CYTOCHROME P450 3A; DIGOXIN; DRUG METABOLIZING ENZYME; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 1 INHIBITOR; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; VERAPAMIL; VINBLASTINE;

CANCER RESISTANCE; COMPUTER PREDICTION; DISCRIMINANT ANALYSIS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG PENETRATION; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG UPTAKE; ENZYME ACTIVITY; ENZYME SPECIFICITY; EVIDENCE BASED MEDICINE; HUMAN; LEARNING ALGORITHM; MACHINE LEARNING; MATHEMATICAL MODEL; MULTIDRUG RESISTANCE; NONHUMAN; PHARMACOPHORE; PHYSICAL CHEMISTRY; PROTEIN DETERMINATION; PROTEIN FUNCTION; PROTEIN TRANSPORT; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW;

ALGORITHMS; ATP-BINDING CASSETTE TRANSPORTERS; COMPUTER SIMULATION; FORECASTING; HUMANS; LIGANDS; MODELS, BIOLOGICAL; NEOPLASM PROTEINS; P-GLYCOPROTEIN; PHARMACEUTICAL PREPARATIONS;

EID: 52649108733     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.9.1167     Document Type: Review

References (79)

1. Mueller M. Available from: http://nutrigene.4t.com/humanabc.htm
2. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Drug Discov 2002;2:48-58
3. Ross DD, Doyle LA. Mining our ABCs: pharmacogenomic approach for evaluating transporter function in cancer drug resistance. Cancer Cell 2004;6:105-7
4. Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 2003;55:3-29
5. van Tellingen O. The importance of drug-transporting P-glycoproteins in toxicology. Toxicol Lett 2001;120:31-41
6. Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987;84:7735-8
7. Schinkel AH, Smit JJM, van Tellingen O, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994;74:491-502
8. Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-drug interactions. J Neuroimmune Pharmacol 2006;1:323-39
9. Kiani J, Imam SZ. Medicinal importance of grapefruit juice and its interaction with various drugs. Nutr J 2007;6:33
10. Wa C-Y, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 2005;22:11-33
11. Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006;44:778-87
12. Szakacs G, Patterson J, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006;5:219-33
13. Feng B, Mills J, Davidson R, et al. In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab Dispos 2008;36(2):268-75
14. Garrigos M, Belehradek J, Mir LM, Orlowski S. Absence of cooperativity for MgATP and verapamil effects on the ATPase activity of P-glycoprotein containing membrane vesicles. Biochem Biophys Res Commun 1993;196:1034-41
15. Polli JW, Wring SA, Humphreys JE, et al. Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 2001;299:620-8
16. Schmid D, Ecker G, Kopp S, et al. Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements. Biochem Pharmacol 1999;58:1447-36
17. Hochman JH, Yamazaki M, Ohe T, JH L. Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with P-glycoprotein. Curr Drug Metab 2002;3:257-73
18. Tiberghien F, Loor F. Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs 1996;7:568-78
19. Zhou H, Wu S, Zhai S, et al. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J Med Chem 2008;51:1242-51
20. Szakacs G, Annereau J-P, Lababidi S, et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 2004;6:129-37
21. Safa AR, Roberts S, Agresti M, Fine RL. Tamoxifen aziridine, a novel affinity probe for P-glycoprotein in multidrug-resistant cells. Biochem Biophys Res Commun 1994;202:606-12
22. Schuetz EG, Beck WT, Schuetz JD. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 1996;49:311-8
23. Zhang X, Ritke M, Yalowich J, et al. P-glycoprotein mediates profound resistance to bisantrene. Oncol Res 1994;6:291-301
24. Humblet C, Marshall GR. Pharmacophore modelling and receptor mapping. Ann Rep Med Chem 1980;15:267-76
25. Wolber G, Seidel T, Bendix F, Langer T. Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discov Today 2008;13:23-9
26. Chang C, Ekins S, Bahadduri P, Swaan PW. Pharmacophore-based discovery of ligands for drug transporters. Adv Drug Deliv Rev 2006;58:1431-50
27. Pearce HL, Winter MA, Beck WT. Structural characteristics of compounds that modulate P-glycoprotein-associated multidrug resistance. Adv Enzyme Regul 1989;30:357-73
28. Pearce HL, Safa AR, Bach NJ, et al. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proc Natl Acad Sci USA 1989;86:5128-32
29. Ecker G, Huber M, Schmid D, Chiba P. The importance of a nitrogen atom in modulators of multidrug resistance. Mol Pharmacol 1999;56:791-6
30. Seelig A. A general pattern for substrate recognition by P-glycoprotein. Eur J Biochem 1998;251:252-61
31. Penzotti JE, Lamb ML, Evensen E, Grootenhuis PDJ. A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein. J Med Chem 2002;45:1737-40
32. Ekins S, Kim RB, Leake BF, et al. Application of three-dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates. Mol Pharmacol 2002;61:974-81
33. Ekins S, Bravi G, Binkley S, et al. Three- and four-dimensional quantitative structure activity relationship analyses of cytochrome P-450 3A4 inhibitors. J Pharmacol Exp Ther 1999;290:429-38
34. Ekins S, Bravi G, Wikel JH, Wrighton SA. Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther 1999;291:424-33
35. Pajeva IK, Wiese M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (Hypothesis). J Med Chem 2002;45:5671-86
36. Ekins S, Kim RB, Leake BF, et al. Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol 2002;61:964-73
37. Garrigues A, Loiseau N, Delaforge M, et al. Characterization of two pharmacophores on the multidrug transporter P-glycoprotein. Mol Pharmacol 2002;62:1288-98
38. Cianchetta G, Singleton RW, Zhang M, et al. A pharmacophore hypothesis for P-glycoprotein substrate recognition using GRIND-based 3D-QSAR. J Med Chem 2005;48:2927-35
39. Langer T, Eder M, Hoffmann RD, et al. Lead identification for modulators of multidrug resistance based on in silico screening with a pharmacophoric feature model. Arch Pharm (Weinheim) 2004;337(6):317-27
40. Chang C, Bahadduri PM, Polli JE, et al. Rapid identification of P-glycoprotein substrates and inhibitors. Drug Metab Dispos 2006;34:1976-84
41. Chang C, Ekins S, Bahadduri P, Swaan PW. Pharmacophore-based discovery of ligands for drug transporters. Adv Drug Deliv Rev 2006;58(12-13):1431-50
42. Li WX, Li L, Eksterowicz J, et al. Significance analysis and multiple pharmacophore models for differentiating P-glycoprotein substrates. J Chem Inf Model 2007;47:2429-38
43. Cramer J, Kopp S, Bates SE, et al. Multispecificity of drug transporters: probing inhibitor selectivity for the human drug efflux transporters ABCB1 and ABCG2. ChemMedChem 2007;2:1783-8
44. Wang YH, Li Y, Yang SL, Yang L. Classification of substrates and inhibitors of P-glycoprotein using unsupervised machine learning approach. J Chem Inf Model 2005;45:750-7
45. Seelig A, Landwojtowicz E. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur J Pharm Sci 2000;12:31-40
46. Didziapetris R, Japertas P, Avdeef A, Petrauskas A. Classification analysis of P-glycoprotein substrate specificity. J Drug Target 2003;11(7):391-406
47. Available from: http://pharma-algorithms.com/adme_boxes.htm
48. Didziapetris R, Japertas P, Petrauskas A. classification SAR (C-SAR) in prediction of P-glycoprotein substrate specificity. Proceedings of the 14th EuroQSAR Symposium (EuroQSAR 2002), Bournemouth, UK
49. Gleeson MP. Generation of a set of simple, interpretable ADMET rules of thumb. J Med Chem 2008;51(4):817-34
50. Adenot M, Lahana R. Blood-brain barrier permeation models: discriminating between potential CNS and non-CNS drugs including P-glycoprotein substrates. J Chem Inf Comput Sci 2004;44:239-48
51. Gombar VK, Polli JW, Humphreys JE, et al. Predicting P-glycoprotein substrates by a quantitative structure-activity relationship model. J Pharm Sci 2004;93:957-68
52. Cabrera MA, González I, Fernández C, et al. A topological substructural approach for the prediction of P-glycoprotein substrates. J Pharm Sci 2006;95:589-606
53. Xue Y, Yap CW, Sun LZ, et al. Prediction of P-glycoprotein substrates by a support vector machine approach. J Chem Inf Comput Sci 2004;44:1497-505
54. Xue Y, Li ZR, et al. Effect of molecular descriptor feature selection in support vector machine classification of pharmacokinetic and toxicological properties of chemical agents. J Chem Ind Model 2004;44:1630-8
55. De Cerqueira Lima P, Golbraikh A, Oloff S, et al. A combinatoriat QSAR modeling of P-glycoprotein substrates. J Chem Inf Model 2006;46(3):1245-54
56. Huang J, Ma G, Muhammad I, Cheng Y. Identifying P-glycoprotein substrates using a support vector machine optimized by a particle swarm. J Chem Inf Model 2007;47:1638-47
57. Chang G, Roth CB. Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ATP) transporters. Science 2001;293:1793-800
58. Chang G. Structure of MsbA from Vibrio Cholerae: a multidrug resistance ABC transporter in a closed conformation. J Mol Biol 2003;330:419-30
59. Chang G. Retraction. Science 2006;314:1875b
60. Ward A, Reyes CL, Yu J, et al. Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc Natl Acad Sci USA 2007;104:19005-10
61. Dawson RJP, Locher KP. Structure of a bacterial multidrug ABC transporter. Nature 2006;443:180-5
62. Dawson RJP, Locher KP. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett 2007;581:935-8
63. Ravna AW, Sylte I, Sager G. Molecular model of the outward facing state of the human P-glycoprotein (ABCB1), and comparison to a model of the human MRP5 (ABCC5). TBiomed 2007;4:33
64. Hazai E, Bikádi Z. Homology modeling of breast cancer resistance protein (ABCG2). J Struct Biol 2008;162:63-74
65. Ravna AW, Sylte I, Sager G. A molecular model of a putative substrate releasing conformation of multidrug resistance protein 5 (MRP5). Eur J Med Chem doi: 10.1016/j.ejmech. 2008.01.015
66. The Innovative Medicines Initiative. Available from: http://imi.europa.eu
67. Vaz R, Klabunde T. Antitargets: prediction and prevention of drug side effects. Edition 1. Weinheim: Wiley-VCH; 2008
68. Zdrazil B, Kaiser D, Kopp S, et al. Similarity-Based Descriptors (SIBAR) as tool for QSAR studies on P-glycoprotein inhibitors: influence of the reference set. QSAR Comb Sci 2007;26:669-78
69. Klein C, Kaiser D, Kopp S, et al. Similarity based SAR (SIBAR) as tool for early ADME profiling. J Comput Aided Mol Des 2002;16:785-93
70. Gregori-Puigjane E, Mestres J. SHED: Shannon Entropy Descriptors from topological feature distributions. J Chem Inf Model 2006;46:1615-22
71. Mestres J, Martin-Couce L, Gregori-Puigjane E, et al. Ligand-based approach to in silice, pharmacology: nuclear receptor profiling. J Chem Inf Model 2006;46:2725-36
72. Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 2007;152:9-20
73. Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: applications to targets and beyond. Br J Pharmacol 2007;152:21-37
74. Paolini GV, Shapland R, van Hoorn W, et al. Global mapping of pharmacological space. Nat Biotechnol 2006;24:243-57
75. Keiser MJ, Roth BL, Armbruster BN, et al. Relating protein pharmacology by ligand chemistry. Nat Biotech 2007;25:197-206
76. Klopman G, Shi LM, Ramu A. Quantitative structure-activity relationship of multidrug resistance reversal agents. Mol Pharmacol 1997;52:323-34
77. Raub TJ. P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol Pharm 2006;3:3-25
78. Cox CD, Breslin MJ, Whitman DB, et al Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by [beta]-fluorination to overcome cellular efflux by P-glycoprotein. Bioorg Med Chem Lett 2007;17:2697-702
79. Nanda KK, Brad Nolt M, Cato MJ, et al. Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of analogous N,N-diisopropyl-2-(pyridine-3-yl)acecamides. Bioorg Med Chem Lett 2006;16:5897-901