278
Views
47
CrossRef citations to date
0
Altmetric
Research Article

Future directions for drug transporter modelling

, , &
Pages 1152-1170 | Received 02 Jul 2007, Accepted 23 Aug 2007, Published online: 22 Sep 2008

References

  • Anderle P, Huang Y, Sadee W. Intestinal membrane transport of drugs and nutrients: Genomics of membrane transporters using expression microarrays. European Journal of Pharmaceutical Science 2004; 21: 17–24
  • Apic G, Ignjatovic T, Boyer S, Russell RB. Illuminating drug discovery with biological pathways. FEBS Letters 2005; 579(8)1872–1877
  • Barabasi A-L, Oltvai ZN. Network biology: understanding the cell's functional organization. Nature Reviews Genetics 2004; 5: 101–113
  • Barnum D, Greene J, Smellie A, Sprague P. Identification of common functional configurations among molecules. Journal of Chemistry Information and Computer Sciences 1996; 36: 563–571
  • Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kaffman M, Noiman S. An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. Journal of Medicine and Chemistry 2006; 49(11)3116–3135
  • Bergström CA. In silico predictions of drug solubility and permeability: Two rate-limiting barriers to oral drug absorption. Basic Clinical Pharmacology and Toxicology 2005; 96(3)156–161
  • Bergström CA, Strafford M, Lazorova L, Avdeef A, Luthman K, Artursson P. Absorption classification of oral drugs based on molecular surface properties. Journal of Medicine and Chemistry 2003; 46(4)558–570
  • Bleasby K, Castle JC, Roberts CJ, Cheng C, Bailey WJ, Sina JF, Kulkarni AV, Hafey MJ, Evers R, Johnson JM, et al. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition. Xenobiotica 2006; 36(10-11)963–988
  • Blesch KS, Gieschke R, Tsukamoto Y, Reigner BG, Burger HU, Steimer JL. Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: The capecitabine experience. Investigational New Drugs 2003; 21(2)195–223
  • Bolger MB, Haworth IS, Yeung AK, Ann D, Von Grafenstein H, Hamm-Alvarez S, Okamoto CT, Kim KJ, Basu SK, Wu S, et al. Structure, function, and molecular modeling approaches to the study of the intestinal dipeptide transporter PepT1. Journal of Pharmaceutical Science 1998; 87(11)1286–1291
  • Carlson HA. Protein flexibility and drug design: How to hit a moving target. Current Opinions in Chemistry and Biology 2002; 6(4)447–452
  • Chang C, Bahadduri PM, Polli JE, Swaan PW, Ekins S. Rapid Identification of P-glycoprotein Substrates and Inhibitors. Drug Metabolism and Disposition 2006a; 34: 1976–1984
  • Chang C, Ekins S, Bahadduri P, Swaan PW. Pharmacophore-based discovery of ligands for drug transporters. Advances in Drug Delivery Reviews 2006b; 58: 1431–1450
  • Chang C, Swaan PW. Computational approaches to modeling drug transporters. European Journal of Pharmaceutical Science 2006a; 27(5)411–424
  • Chang C, Swaan PW. Computer optimization of biopharmaceutical properties. Computer applications in pharmaceutical research and development, S Ekins. Wiley, Hoboken 2006b; 495–512
  • Charnick SB, Kawai R, Nedelman JR, Lemaire M, Niederberger W, Sato H. Perspectives in pharmacokinetics. Physiologically based pharmacokinetic modeling as a tool for drug development. Journal of Pharmacokinetics and Biopharmaceutics 1995; 23(2)217–229
  • Chiba P, Mihalek I, Ecker GF, Kopp S, Lichtarge O. Role of transmembrane domain/transmembrane domain interfaces of P-glycoprotein (ABCB1) in solute transport. Convergent information from photoaffinity labeling, site directed mutagenesis and in silico importance prediction. Current Medicine and Chemistry 2006; 13(7)793–805
  • Claussen H, Buning C, Rarey M, Lengauer T. FlexE: efficient molecular docking considering protein structure variations. Journal of Molecular Biology 2001; 308(2)377–395
  • De Buck SS, Sinha VK, Fenu LA, Gilissen RA, Mackie CE, Nijsen MJ. The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools. Drug Metabolism and Disposition 2007; 35(4)649–659
  • Dimitrov S, Dimitrova G, Pavlov T, Dimitrova N, Patlewicz G, Niemela J, Mekenyan O. A stepwise approach for defining the applicability domain of SAR and QSAR models. Journal of Chemistry and Inf Models 2005; 45(4)839–849
  • Ecker GF. In silico screening of promiscuous targets and antitargets. Chemistry Today 2005; 23: 39–42
  • Ecker GF, Chiba P. QSAR-studies on drug transporters involved in toxicology. Computational toxicology: Risk assessment for pharmaceutical and environmental chemicals, S Ekins. Wiley, Hoboken 2007; 295–314
  • Ekins S. Systems-ADME/Tox: Resources and network approaches. Journal of Pharmacology and Toxicology Methods 2006; 53(1)38–66
  • Ekins S, Abramowitz DL. A systems-biology view of drug transporters. Transporters as drug carriers, G Ecker, P Chiba, Hoboken 2007, Wiley (in press)
  • Ekins S, Andreyev S, Ryabov A, Kirillov E, Rakhmatulin EA, Sorokina S, Bugrim A, Nikolskaya T. A combined approach to drug metabolism and toxicity assessment. Drug Metabolism and Disposition 2006a; 34: 495–503
  • Ekins S, Balakin KV, Savchuk N, Ivanenkov Y. Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning, Kohonen and Sammon mapping Techniques. Journal of Medicine and Chemistry 2006b; 49: 5059–5071
  • Ekins S, Bugrim A, Nikolsky Y, Nikolskaya T. Systems biology: applications in drug discovery. Drug discovery handbook, S Gad. Wiley, New York, NY 2005a; 123–183
  • Ekins S, Durst GL, Stratford RE, Thorner DA, Lewis R, Loncharich RJ, Wikel JH. Three dimensional quantitative structure permeability relationship analysis for a series of inhibitors of rhinovirus replication. Journal of Chemistry Inf and Computer Science 2001; 41: 1578–1586
  • Ekins S, Johnston JS, Bahadduri P, D'Souzza M, Ray A, Chang C, Swaan PW. In vitro and pharmacophore based discovery of novel hPEPT1 inhibitors. Pharmacology Research 2005b; 22: 512–517
  • Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz E, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, et al. Application of three dimensional quantitative structure–activity relationships of P-glycoprotein inhibitors and substrates. Molecular Pharmacology 2002a; 61: 974–981
  • Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz E, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, et al. Three dimensional quantitative structure–activity relationships of inhibitors of P-glycoprotein. Molecular Pharmacology 2002b; 61: 964–973
  • Ekins S, Kirillov E, Rakhmatulin E, Nikolskaya T. A novel method for visualizing nuclear hormone receptor networks relevant to drug metabolism. Drug Metabolism and Disposition 2005c; 33: 474–481
  • Ekins S, Nikolsky Y, Nikolskaya T. Techniques: Application of systems biology to absorption, distribution, metabolism, excretion, and toxicity. Trends in Pharmacology Science 2005d; 26: 202–209
  • Ekins S, Shimada J, Chang C. Application of data mining approaches to drug delivery. Advances in Drug Delivery Review 2006c; 58(12–13)1409–1430
  • Enyedy IJ, Sakamuri S, Zaman WA, Johnson KM, Wang S. Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors. Bioorganic Medicine and Chemistry Letters 2003; 13(3)513–517
  • Enyedy IJ, Zaman WA, Sakamuri S, Kozikowski AP, Johnson KM, Wang S. Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors. Bioorganic Medicine and Chemistry Letters 2001; 11(9)1113–1118
  • Gerlowski LE, Jain RK. Physiologically based pharmacokinetic modeling: Principles and applications. Journal of Pharmaceutical Science 1983; 72(10)1103–1127
  • Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Reviews Cancer 2002; 2(1)48–58
  • Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA. The ABCs of solute carriers: Physiological, pathological and therapeutic implications of human membrane transport proteins. Introduction. Pflugers Archives 2004; 447(5)465–468
  • Higgins CF. Multiple molecular mechanisms for multidrug resistance transporters. Nature 2007; 446(7137)749–757
  • Higgins CF, Callaghan R, Linton KJ, Rosenberg MF, Ford RC. Structure of the multidrug resistance P-glycoprotein. Seminars in Cancer Biology 1997; 8(3)135–142
  • Hoffman BT, Kopajtic T, Katz JL, Newman AH. 2D QSAR modeling and preliminary database searching for dopamine transporter inhibitors using genetic algorithm variable selection of Molconn Z descriptors. Journal of Medicine and Chemistry 2000; 43(22)4151–4159
  • Holz M, Fahr A. Compartment modeling. Advances in Drug Delivery Review 2001; 48(2–3)249–264
  • Huang Y, Anderle P, Bussey KJ, Barbacioru C, Shankavaram U, Dai Z, Reinhold WC, Papp A, Weinstein JN, Sadee W. Membrane transporters and channels: Role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Research 2004; 64(12)4294–4301
  • Jang SH, Wientjes MG, Au JL. Interdependent effect of P-glycoprotein-mediated drug efflux and intracellular drug binding on intracellular paclitaxel pharmacokinetics: Application of computational modeling. Journal of Pharmacology and Experimental Therapy 2003; 304(2)773–780
  • Kairys V, Fernandes MX, Gilson MK. Screening drug-like compounds by docking to homology models: A systematic study. Journal of Chemistry and Inf Models 2006; 46(1)365–379
  • Kaiser D, Terfloth L, Kopp S, Schulz J, de Laet R, Chiba P, Ecker GF, Gasteiger J. Self-organizing maps for identification of new inhibitors of P-glycoprotein. Journal of Medicine and Chemistry 2007; 50(7)1698–1702
  • Kaiser D, Zdrazil B, Ecker GF. Similarity-based descriptors (SIBAR) — a tool for safe exchange of chemical information?. Journal of Computer-Aided Molecular Design 2005; 19(9–10)687–692
  • Kaminski JJ, Rane DF, Snow ME, Weber L, Rothofsky ML, Anderson SD, Lin SL. Identification of novel farnesyl protein transferase inhibitors using three-dimensional searching methods. Journal of Medicinal Chemistry. 1997; 40: 4103–4112
  • Kamiya K, Niwa R, Mitcheson JS, Sanguinetti MC. Molecular determinants of HERG channel block. Molecular Pharmacology 2006; 69(5)1709–1716
  • Keizers PH, de Graaf C, de Kanter FJ, Oostenbrink C, Feenstra KA, Commandeur JN, Vermeulen NP. Metabolic regio- and stereoselectivity of cytochrome P450 2D6 towards 3,4-methylenedioxy-N-alkylamphetamines: In silico predictions and experimental validation. Journal of Medicine and Chemistry 2005; 48(19)6117–6127
  • Kemp CA, Flanagan JU, Van Eldik AJ, Marechal JD, Wolf CR, Roberts GC, Paine MJ, Sutcliffe MJ. Validation of model of cytochrome P450 2D6: An in silico tool for predicting metabolism and inhibition. Journal of Medicine and Chemistry 2004; 47(22)5340–5346
  • Khandelwal A, Bahadduri P, Chang C, Polli JE, Swaan P, Ekins S. Computational models to assign biopharmaceutics drug disposition classification from molecular structure 2007, Pharmaceutical Research (in press)
  • Kim R, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. Journal of Clinical Investigation 1998; 101: 289–294
  • Klein C, Kaiser D, Kopp S, Chiba P, Ecker GF. Similarity based SAR (SIBAR) as tool for early ADME profiling. Journal of Computer-Aided Molecular Design 2002; 16(11)785–793
  • Langer T, Eder M, Hoffmann RD, Chiba P, Ecker GF. Lead identification for modulators of multidrug resistance based on in silico screening with a pharmacophoric feature model. Arch Pharm (Weinheim) 2004; 337(6)317–327
  • Lee TS, Eid T, Mane S, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NC. Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy. Acta Neuropathologica (Berlin) 2004; 108(6)493–502
  • Li YF, Polgar O, Okada M, Esser L, Bates SE, Xia D. Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: A molecular modeling study. Journal of Molecular Graph Modelling 2007; 25(6)837–851
  • Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. European Journal of Pharmacology and Biopharmacology 2004; 58(2)265–278
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advances in Drug Delivery Reviews 1997; 23: 3–25
  • Marechal JD, Yu J, Brown S, Kapelioukh I, Rankin EM, Wolf CR, Roberts GC, Paine MJ, Sutcliffe MJ. silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by co-medications commonly used by patients with cancer. Drug Metabolism and Disposition 2006; 34: 534–538
  • Martin YC. 3D database searching in drug design. Journal of Medicinal Chemistry 1992; 35: 2145–2154
  • Martin YC, Bures MG, Danaher EA, DeLazzer J, Lico I, Pavlik PA. A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists. Journal of Computer-Aided Molecular Design 1993; 7(1)83–102
  • Meredith D, Price RA. Molecular modeling of PepT1 — towards a structure. Journal of Membrane Biology 2006; 213(2)79–88
  • Neyfakh AA. Mystery of multidrug transporters: The answer can be simple. Molecular Microbiology 2002; 44(5)1123–1130
  • Nicklaus MC, Neamati N, Hong H, Mazumder A, Sunder S, Chen J, Milne GWA, Pommier Y. HIV-1 integrase pharmacophore: Discovery of inhibitors through three-dimensional database searching. Journal of Medicinal Chemistry 1997; 40: 920–929
  • Nikitin A, Egorov S, Daraselia N, Mazo I. Pathway studio — the analysis and navigation of molecular networks. Bioinformatics 2003; 19: 2155–2157
  • O’Brien SE, de Groot MJ. Greater than the sum of its parts: Combining models for useful ADMET prediction. Journal of Medicine and Chemistry 2005; 48(4)1287–1291
  • Oshiro C, Bradley EK, Eksterowicz J, Evensen E, Lamb ML, Lanctot JK, Putta S, Stanton R, Grootenhuis PD. Performance of 3D-database molecular docking studies into homology models. Journal of Medicine and Chemistry 2004; 47(3)764–767
  • Osterberg F, Aqvist J. Exploring blocker binding to a homology model of the open hERG K+ channel using docking and molecular dynamics methods. FEBS Letters 2005; 579(13)2939–2944
  • Ozawa N, Shimizu T, Morita R, Yokono Y, Ochiai T, Munesada K, Ohashi A, Aida Y, Hama Y, Taki K, et al. Transporter database, TP-Search: A web-accessible comprehensive database for research in pharmacokinetics of drugs. Pharmacology Research 2004; 21(11)2133–2134
  • Pearce HL, Safa AR, Bach NJ, Winter MA, Cirtain MC, Beck WT. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proceedings of the National Academy of Sciences, USA 1989; 86: 5128–5132
  • Pearce HL, Winter MA, Beck WT. Structural characteristics of compounds that modulate P-glycoprotein-associated multidrug resistance. Advance in Enzyme Regulation 1990; 30: 357–373
  • Pearlstein RA, Vaz RJ, Kang J, Chen X-L, Preobrazhenskaya M, Shchekotikhin AE, Korolev AM, Lysenkova LN, Miroshnikova OV, Hendrix J, et al. Characterization of HERG Potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorganic Medicine and Chemistry 2003; 13: 1829–1835
  • Penzotti JE, Lamb ML, Evensen E, Grootenhuis PD. A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein. Journal of Medicine and Chemistry 2002; 45(9)1737–1740
  • Perry JL, Dembla-Rajpal N, Hall LA, Pritchard JB. A three-dimensional model of human organic anion transporter 1: Aromatic amino acids required for substrate transport. Journal of Biology and Chemistry 2006a; 281(49)38071–38079
  • Perry M, Stansfeld PJ, Leaney J, Wood C, de Groot MJ, Leishman D, Sutcliffe MJ, Mitcheson JS. Drug binding interactions in the inner cavity of HERG channels: Molecular insights from structure–activity relationships of clofilium and ibutilide analogs. Molecular Pharmacology 2006b; 69(2)509–519
  • Pleban K, Ecker GF. Inhibitors of p-glycoprotein — lead identification and optimisation. Mini Reviews in Medicinal Chemistry 2005; 5(2)153–163
  • Pleban K, Kaiser D, Kopp S, Peer M, Chiba P, Ecker GF. Targeting drug-efflux pumps — a pharmacoinformatic approach. Acta Biochimica Polonica 2005a; 52(3)737–740
  • Pleban K, Kopp S, Csaszar E, Peer M, Hrebicek T, Rizzi A, Ecker GF, Chiba P. P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach. Molecular Pharmacology 2005b; 67(2)365–374
  • Rebitzer S, Annibali D, Kopp S, Eder M, Langer T, Chiba P, Ecker GF, Noe CR. In silico screening with benzofurane- and benzopyrane-type MDR-modulators. Farmaco 2003; 58(3)185–191
  • Rosenberg MF, Callaghan R, Ford RC, Higgins CF. Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis. Journal of Biology and Chemistry 1997; 272(16)10685–10694
  • Rosenberg MF, Kamis AB, Callaghan R, Higgins CF, Ford RC. Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding. Journal of Biology and Chemistry 2003; 278(10)8294–8299
  • Rosenberg MF, Velarde G, Ford RC, Martin C, Berridge G, Kerr ID, Callaghan R, Schmidlin A, Wooding C, Linton KJ, et al. Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO Journal 2001; 20(20)5615–5625
  • Saier MH, Jr, Tran CV, Barabote RD. TCDB: The Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Research 2006; 34[(Special Issue: ‘Database’)D181–D186
  • Schapira M, Raaka BM, Samuels HH, Abagyan R. Rational discovery of novel nuclear hormone receptor antagonists. Proceedings of the National Academy of Sciences, USA 2000; 97: 1008–1013
  • Schumacher MA, Miller MC, Brennan RG. Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein. EMBO Journal 2004; 23(15)2923–2930
  • Schumacher MA, Miller MC, Grkovic S, Brown MH, Skurray RA, Brennan RG. Structural mechanisms of QacR induction and multidrug recognition. Science 2001; 294(5549)2158–2163
  • Schwarz UI, Gramatte T, Krappweis J, Oertel R, Kirch W. P-glycoprotein inhibitor erythromycin increases oral bioavailability of talinolol in humans. International Journal of Clinical Pharmacology and Therapy 2000; 38(4)161–167
  • Seelig A. How does P-glycoprotein recognize its substrates?. International Journal of Clinical Pharmacology and Therapy 1998; 36: 50–54
  • Sheridan RP, Feuston BP, Maiorov VN, Kearsley SK. Similarity to molecules in the training set is a good discriminator for prediction accuracy in QSAR. Journal of Chemistry Inf and Computer Science 2004; 44(6)1912–1928
  • Sherman W, Beard HS, Farid R. Use of an induced fit receptor structure in virtual screening. Chemical Biology and Drug Design 2006; 67(1)83–84
  • Shoichet BK. Virtual screening of chemical libraries. Nature 2004; 432(7019)862–865
  • So S-S, Karplus M. A comparative study of ligand–receptor complex binding affinity prediction methods based on glycogen phosphorylase inhibitors. Journal of Computer-Aided Molecular Design 1999; 13: 243–258
  • Sprague PW. Automated chemical hypothesis generation and database searching with Catalyst. Perspectives in Drug Discovery Design 1995; 3: 1–20
  • Sprague PW, Hoffman R. CATALYST pharmacophore models and their utility as queries for searching 3D databases. Computer-assisted lead finding and optimization, H Van de Waterbeemd, B Testa, G Folkers. Helvetica Chimica Acta, Basle 1997; 225–240
  • Stansfeld PJ, Gedeck P, Gosling M, Cox B, Mitcheson JS, Sutcliffe MJ. Drug block of the hERG potassium channel: Insight from modeling. Proteins 2007; 68(2)568–580
  • Stouch TR, Gudmundsson O. Progress in understanding the structure–activity relationships of P-glycoprotein. Advances in Drug Delivery Reviews 2002; 54: 315–328
  • Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda GI. Can we estimate the accuracy of ADME-Tox predictions?. Drug Discovery Today 2006; 11(15–16)700–707
  • Tubic M, Wagner D, Spahn-Langguth H, Bolger MB, Langguth P. In silico modeling of non-linear drug absorption for the P-gp substrate talinolol and of consequences for the resulting pharmacodynamic effect. Pharmacology Research 2006; 23(8)1712–1720
  • Veng-Pedersen P. Noncompartmentally-based pharmacokinetic modeling. Advances in Drug Delivery Review 2001; 48(2–3)265–300
  • Venkatakrishnan K, Tseng E, Nelson FR, Rollema H, French JL, Kaplan IV, Horner WE, Gibbs MA. CNS pharmacokinetics of the Mdr1 P-glycoprotein substrate Cp-615,003: inter-site differences and implications for human receptor occupancy projections from CSF exposures. Drug Metabolism and Disposition. 2007; 35: 1341–1349
  • Wang S, Sakamuri S, Enyedy IJ, Kozikowski AP, Deschaux O, Bandyopadhyay BC, Tella SR, Zaman WA, Johnson KM. Discovery of a novel dopamine transporter inhibitor, 4-hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone, as a potential cocaine antagonist through 3D-database pharmacophore searching. Molecular modeling, structure–activity relationships, and behavioral pharmacological studies. Journal of Medicine and Chemistry 2000; 43(3)351–360
  • Wang S, Zaharevitz DW, Sharma R, Marquez VE, Lewin NE, Du L, Blumberg PM, Milne GWA. The discovery of novel, structurally diverse protein kinase C agonists through computer 3D-database pharmacophore search. Molecular modeling studies. Journal of Medicine and Chemistry 1994; 37: 4479–4489
  • Wu CY, Benet LZ. Predicting drug disposition via application of BCS: Transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharmacology Research 2005; 22(1)11–23
  • Yan Q, Sadee W. Human membrane transporter database: a web-accessible relational database for drug transport studies and pharmacogenomics. AAPS PharmSci 2000; 2: E20
  • Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, Dalton JT, Swaan PW. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharmacology Research 2003; 20(11)1794–1803
  • Yu J, Paine MJ, Marechal JD, Kemp CA, Ward CJ, Brown S, Sutcliffe MJ, Roberts GC, Rankin EM, Wolf CR. In silico prediction of drug binding to CYP2D6: Identification of a new metabolite of metoclopramide. Drug Metabolism and Disposition 2006; 34(8)1386–1392
  • Zdrazil B, Kaiser D, Kopp S, Chiba P, Ecker GF. Similarity-based descriptors (SIBAR) as tool for QSAR-studies on P-glycoprotein inhibitors: Influence of the reference set. QSAR and Combination Chemistry 2007; 26: 669–678
  • Zhang EY, Knipp GT, Ekins S, Swaan PW. Structural biology and function of solute transporters: Implications for identifying and designing substrates. Drug Metabolism Reviews 2002a; 34: 709–750
  • Zhang EY, Phelps MA, Cheng C, Ekins S, Swaan PW. Modeling of active transport systems. Advances in Drug Delivery Reviews 2002b; 54: 329–354
  • Zhang X, Shirahatti NV, Mahadevan D, Wright SH. A conserved glutamate residue in transmembrane helix 10 influences substrate specificity of rabbit OCT2 (SLC22A2). Journal of Biology and Chemistry 2005; 280(41)34813–34822
  • Zheleznova EE, Markham PN, Neyfakh AA, Brennan RG. Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter. Cell 1999; 96(3)353–362

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.