Prediction of promiscuous p-glycoprotein inhibition using a novel machine learning scheme

PLoS ONE

Volumn 7, Issue 3, 2012, Pages

  Leong, Max K ^a,b   Chen, Hong Bin ^a   Shih, Yu Hsuan ^a  

^a NATIONAL DONG HWA UNIVERSITY   (Taiwan)

^b MENNONITE CHRISTIAN HOSPITAL   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN P; ABCB1 PROTEIN, HUMAN;

ACCURACY; ARTICLE; BINDING AFFINITY; COMPUTER MODEL; COMPUTER PREDICTION; CONTROLLED STUDY; DRUG DESIGN; MACHINE LEARNING; PHARMACOPHORE; PHARMACOPHORE ENSEMBLE SUPPORT VECTOR MACHINE; SUPPORT VECTOR MACHINE; THEORETICAL MODEL; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; DRUG ANTAGONISM; DRUG DEVELOPMENT; EVALUATION; HUMAN; MOUSE; PROTEIN CONFORMATION; VALIDATION STUDY;

ANIMALS; COMPUTER SIMULATION; DRUG DESIGN; DRUG DISCOVERY; HUMANS; MICE; MODELS, MOLECULAR; P-GLYCOPROTEIN; PROTEIN CONFORMATION; SUPPORT VECTOR MACHINES;

EID: 84863385532     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0033829     Document Type: Article

References (75)

1. Schinkel AH, Jonker JW, (2003) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliver Rev 55: 3-29.
2. Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, et al. (1987) Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 84: 265-269.
3. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, et al. (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84: 7735-7738.
4. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM, (2003) P-glycoprotein: from genomics to mechanism. Oncogene 22: 7468-7485.
5. Gottesman MM, Pastan I, (2003) Biochemistry of Multidrug Resistance Mediated by the Multidrug Transporter. Ann Rev Biochem 62: 385-427.
6. Doppenschmitt S, Spahn-Langguth H, Regårdh CG, Langguth P, (1999) Role of P-glycoprotein-mediated secretion in absorptive drug permeabiity: An approach using passive membrane permeability and affinity to P-glycoprotein. J PharmSci 88: 1067-1072.
7. Bansal T, Jaggi M, Khar RK, Talegaonkar S, (2009) Status of Flavonols as P-Glycoprotein Inhibitors in Cancer Chemotherapy. Curr Cancer Ther Rev 5: 89-99.
8. Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, et al. (2001) In Vitro and in Vivo Reversal of P-Glycoprotein-mediated Multidrug Resistance by a Novel Potent Modulator, XR9576. Cancer Res 61: 749-758.
9. Ambudkar S, Dey S, Hrycyna C, Ramachandra M, Pastan I, et al. (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol pp. 361-398.
10. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, et al. (1998) The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 101: 289-294.
11. Löscher W, Potschka H, (2005) Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 6: 591-602.
12. Jansen G, Scheper R, Dijkmans B, (2003) Multidrug resistance proteins in rheumatoid arthritis, role in disease-modifying antirheumatic drug efficacy and inflammatory processes: an overview. Scand J Rheumatol 32: 325-336.
13. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM, (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5: 219-234.
14. Solit DB, Rosen N, (2006) Hsp90: A Novel Target for Cancer Therapy. Curr Top Med Chem 6: 1205-1214.
15. Biamonte MA, Van de Water R, Arndt JW, Scannevin RH, Perret D, et al. (2009) Heat Shock Protein 90: Inhibitors in Clinical Trials. J Med Chem 53: 3-17.
16. Taldone T, Gozman A, Maharaj R, Chiosis G, (2008) Targeting Hsp90: small-molecule inhibitors and their clinical development. Curr Opin Pharmacol 8: 370-374.
17. Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, et al. (2009) Update on Hsp90 Inhibitors in Clinical Trial. Curr Top Med Chem 9: 1479-1492.
18. Coley HM, (2010) Overcoming Multidrug Resistance in Cancer: Clinical Studies of P-Glycoprotein Inhibitors In: Zhou J, editors. Multi-Drug Resistance in Cancer New York Humana Press pp. 341-358.
19. Shukla S, Wu C-P, Ambudkar SV, (2008) Development of inhibitors of ATP-binding cassette drug transporters - present status and challenges. Expert Opin Drug Metab Toxicol 4: 205-223.
20. Leonard GD, Fojo T, Bates SE, (2003) The Role of ABC Transporters in Clinical Practice. Oncologist 8: 411-424.
21. Lin JH, (2003) Drug-drug interaction mediated by inhibition and induction of P-glycoprotein. Adv Drug Deliv Rev 55: 53-81.
22. Greiner B, Eichelbaum M, Fritz P, Kreichgauer H-P, von Richter O, et al. (1999) The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 104: 147-153.
23. Crowley E, McDevitt CA, Callaghan R, (2010) Generating Inhibitors of P-Glycoprotein: Where to, Now? In: Zhou J, editors. Multi-Drug Resistance in Cancer New York Humana Press pp. 405-432.
24. Ekins S, Mestres J, Testa B, (2007) In silico pharmacology for drug discovery: applications to targets and beyond. Br J Pharmacol 152: 21-37.
25. Chang C, Ekins S, (2006) Pharmacophores for Human ADME/Tox-related Proteins. In: Langer T, Hoffmann RD, editors. Pharmacophores and Pharmacophore Searches Weinheim, Germany Wiley pp. 299-324.
26. Zhou H, Wu S, Zhai S, Liu A, Sun Y, et al. (2008) Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J Med Chem 51: 1242-1251.
27. Chang C, Bahadduri PM, Polli JE, Swaan PW, Ekins S, (2006) Rapid Identification of P-glycoprotein Substrates and Inhibitors. Drug Metab Dispos 34: 1976-1984.
28. Langer T, Eder M, Hoffmann RD, Chiba P, Ecker GF, (2004) Lead identification for modulators of multidrug resistance based on in silico screening with a pharmacophoric feature model. Arch Pharm 337: 317-327.
29. Pajeva IK, Wiese M, (2002) Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J Med Chem 45: 5671-5686.
30. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, et al. (2002) Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol 61: 964-973.
31. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, et al. (2002) Application of three-dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates. Mol Pharmacol 61: 974-981.
32. Pajeva I, Globisch C, Fleischer R, Tsakovska I, Wiese M, (2005) Molecular Modeling of P-Glycoprotein and Related Drugs. Med Chem Res 14: 106-117.
33. Palmeira A, Rodrigues F, Sousa E, Pinto M, Vasconcelos M, et al. (2010) Pharmacophore-Based Screening as a Clue for the Discovery of New P-Glycoprotein Inhibitors. In: Rocha M, Riverola F, Shatkay H, Corchado J, editors. Advances in Bioinformatics Berlin Springer Berlin/Heidelberg pp. 175-180.
34. Pleban K, Kaiser D, Kopp S, Peer M, Chiba P, et al. (2005) Targeting drug-efflux pumps-a pharmacoinformatic approach. Acta Biochim Pol 52: 737-740.
35. Ekins S, (2004) Predicting undesirable drug interactions with promiscuous proteins in silico. Drug Discov Today 9: 276-285.
36. Loo TW, Bartlett MC, Clarke DM, (2003) 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 278: 13603-13606.
37. Bahadduri P, Polli J, Swaan P, Ekins S, (2010) Targeting Drug Transporters - Combining In Silico and In Vitro Approaches to Predict In Vivo. In: Yan Q, editors. Membrane Transporters in Drug Discovery and Development: Methods and Protocols New York Humana Press pp. 65-103.
38. Ward A, Reyes CL, Yu J, Roth CB, Chang G, (2007) Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc Natl Acad Sci 104: 19005-19010.
39. Stockner T, de Vries SJ, Bonvin AM, Ecker GF, Chiba P, (2009) Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains. FEBS J 276: 964-972.
40. Ravna A, Sylte I, Sager G, (2009) Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure. Theoretical Biology and Medical Modelling 6: 20.
41. Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, et al. (2009) Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 323: 1718-1722.
42. Gutmann DAP, Ward A, Urbatsch IL, Chang G, van Veen HW, (2010) Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1. Trends Biochem Sci 35: 36-42.
43. Ecker GF, (2010) QSAR Studies on ABC Transporter - How to Deal with Polyspecificity. In: Ecker G, Chiba P, editors. Transporters as Drug Carriers: Structure, Function, Substrates Weinheim, Germany Wiley-VCH Verlag GmbH & Co. KGaA pp. 195-214.
44. Varma MVS, Ashokraj Y, Dey CS, Panchagnula R, (2003) P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol Res 48: 347-359.
45. Globisch C, Pajeva IK, Wiese M, (2008) Identification of Putative Binding Sites of P-glycoprotein Based on its Homology Model. Chem Med Chem 3: 280-295.
46. Penzotti JE, Lamb ML, Evensen E, Grootenhuis PDJ, (2002) A Computational Ensemble Pharmacophore Model for Identifying Substrates of P-Glycoprotein. J Med Chem 45: 1737-1740.
47. Li W-X, Li L, Eksterowicz J, Ling XB, Cardozo M, (2007) Significance analysis and multiple pharmacophore models for differentiating P-glycoprotein substrates. J Chem Inf Model 47: 2429-2438.
48. Leong MK, (2007) A Novel Approach Using Pharmacophore Ensemble/Support Vector Machine (PhE/SVM) for Prediction of hERG Liability. Chem Res Toxicol 20: 217-226.
49. Chen C-N, Shih Y-H, Ding Y-L, Leong MK, (2011) Predicting Activation of the Promiscuous Human Pregnane X Receptor by Pharmacophore Ensemble/Support Vector Machine Approach. Chem Res Toxicol 24: 1765-1778.
50. Leong MK, Chen Y-M, Chen H-B, Chen P-H, (2009) Development of a New Predictive Model for Interactions with Human Cytochrome P450 2A6 Using Pharmacophore Ensemble/Support Vector Machine (PhE/SVM) Approach. Pharm Res 26: 987-1000.
51. Leong MK, Chen T-H, (2008) Prediction of cytochrome P450 2B6-substrate interactions using pharmacophore ensemble/support vector machine (PhE/SVM) approach. Med Chem 4: 396-406.
52. Chiba P, Holzer W, Landau M, Bechmann G, Lorenz K, et al. (1998) Substituted 4-Acylpyrazoles and 4-Acylpyrazolones: Synthesis and Multidrug Resistance-Modulating Activity. J Med Chem 41: 4001-4011.
53. Klein C, Kaiser D, Kopp S, Chiba P, Ecker GF, (2002) Similarity based SAR (SIBAR) as tool for early ADME profiling. J Comput-Aided Mol Des 16: 785-793.
54. Hiessböck R, Wolf C, Richter E, Hitzler M, Chiba P, et al. (1999) Synthesis and in Vitro Multidrug Resistance Modulating Activity of a Series of Dihydrobenzopyrans and Tetrahydroquinolines. J Med Chem 42: 1921-1926.
55. Foloppe N, Chen I-J, (2009) Conformational Sampling and Energetics of Drug-Like Molecules. Curr Med Chem 16: 3381-3413.
56. Chang G, Guida WC, Still WC, (1989) An internal-coordinate Monte Carlo method for searching conformational space. J Am Chem Soc 111: 4379-4386.
57. Kolossvary I, Guida WC, (1996) Low mode search. An efficient, automated computational method for conformational analysis: Application to cyclic and acyclic alkanes and cyclic peptides. J Am Chem Soc 118: 5011-5019.
58. Halgren TA, (1996) Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem 17: 490-519.
59. Still WC, Tempczyk A, Hawley RC, Hendrickson T, (1990) Semianalytical treatment of solvation for molecular mechanics and dynamics. J Am Chem Soc 112: 6127-6129.
60. Zou J, Xie H-Z, Yang S-Y, Chen J-J, Ren J-X, et al. (2008) Towards more accurate pharmacophore modeling: Multicomplex-based comprehensive pharmacophore map and most-frequent-feature pharmacophore model of CDK2. J Mol Graph Model 27: 430-438.
61. Sprague PW, (1995) Automated chemical hypothesis generation and database searching with Catalyst. Perspect Drug Discovery Des 3: 1-20.
62. Li H, Sutter J, Hoffmann R, (2000) HypoGen: An Automated System for Generating 3D Predictive Pharmacophore Models. In: Güner OF, editors. Pharmacophore Perception, Development, and Use in Drug Design La Jolla, California International University Line pp. 171-189.
63. Labrie P, Maddaford SP, Lacroix J, Catalano C, Lee DKH, et al. (2006) In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450. Bioorg Med Chem 14: 7972-7987.
64. Kurogi Y, Güner OF, (2001) Pharmacophore Modeling and Three-dimensional Database Searching for Drug Design Using Catalyst. Curr Med Chem 8: 1035-1055.
65. Evans DA, Doman TN, Thorner DA, Bodkin MJ, (2007) 3D QSAR methods: Phase and Catalyst compared. J Chem Inf Model 47: 1248-1257.
66. Leong MK, Chen Y-M, Chen T-H, (2009) Prediction of Human Cytochrome P450 2B6-Substrate Interactions Using Hierarchical Support Vector Regression Approach. J Comput Chem 30: 1899-1909.
67. Golbraikh A, Shen M, Xiao Z, Xiao Y-D, Lee K-H, et al. (2003) Rational selection of training and test sets for the development of validated QSAR models. J Comput-Aided Mol Des 17: 241-253.
68. Benfenati E, Chrétien JR, Giuseppina Gini, Piclin N, Pintore M, et al. (2007) Validation of the models. In: Benfenati E, editors. Quantitative Structure-Activity Relationships (QSAR) for Pesticide Regulatory Purposes Amsterdam Elsevier pp. 185-199.
69. Roy PP, Roy K, (2008) On Some Aspects of Variable Selection for Partial Least Squares Regression Models. QSAR Comb Sci 27: 302-313.
70. Gramatica P, Giani E, Papa E, (2007) Statistical external validation and consensus modeling: A QSPR case study for Koc prediction. J Mol Graph Model 25: 755-766.
71. Martin C, Berridge G, Higgins CF, Mistry P, Charlton P, et al. (2000) Communication between Multiple Drug Binding Sites on P-glycoprotein. Mol Pharmacol 58: 624-632.
72. Wang Y-H, Li Y, Yang S-L, Yang L, (2005) An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network. J Comput-Aided Mol Des 19: 137-147.
73. Zalloum HM, Taha MO, (2008) Development of predictive in silico model for cyclosporine- and aureobasidin-based P-glycoprotein inhibitors employing receptor surface analysis. J Mol Graph Model 27: 439-451.
74. Chen L, Li Y, Zhao Q, Peng H, Hou T, (2011) ADME Evaluation in Drug Discovery. 10. Predictions of P-Glycoprotein Inhibitors using Recursive Partitioning and Naïve Bayesian Classification Techniques. Mol Pharmaceutics 8: 889-900.
75. Labrie P, Maddaford SP, Fortin S, Rakhit S, Kotra LP, et al. (2006) A comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of anthranilamide derivatives that are multidrug resistance modulators. J Med Chem 49: 7646-7660.