Toward in silico structure-based ADMET prediction in drug discovery

Drug Discovery Today

Volumn 17, Issue 1-2, 2012, Pages 44-55

  Moroy, Gautier ^a   Martiny, Virginie Y ^a   Vayer, Philippe ^b   Villoutreix, Bruno O ^a   Miteva, Maria A ^a  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANALGESIC AGENT; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIALLERGIC AGENT; ANTIARRHYTHMIC AGENT; ANTIBIOTIC AGENT; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ANTIDIABETIC AGENT; ANTIFUNGAL AGENT; ANTIHYPERTENSIVE AGENT; ANTINEOPLASTIC AGENT; ANTIOXIDANT; ANTIRETROVIRUS AGENT; ANTIULCER AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BUFURALOL; CHLORPROPAMIDE; DESIPRAMINE; DICLOFENAC; FLUOXETINE; METOPROLOL; NATEGLINIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PACTIMIBE; PHENYTOIN; QUININE; STEROID; TAMOXIFEN; UNINDEXED DRUG; WARFARIN;

BINDING SITE; CHEMICAL MODIFICATION; COMPUTER MODEL; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG STRUCTURE; GENETIC POLYMORPHISM; HUMAN; HYDROGEN BOND; LIGAND BINDING; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TERTIARY STRUCTURE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW;

ABSORPTION; ANIMALS; DRUG DISCOVERY; DRUG TOXICITY; HUMANS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; PHARMACOLOGY; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84855861782     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2011.10.023     Document Type: Review

References (113)

1. C. Merlot Computational toxicology - a tool for early safety evaluation Drug Discov. Today 15 2010 16 22
2. L. Michielan, and S. Moro Pharmaceutical perspectives of nonlinear QSAR strategies J. Chem. Inf. Model. 50 2010 961 978
3. M.P. Gleeson In silico ADME models: a general assessment of their utility in drug discovery applications Curr. Top. Med. Chem. 11 2011 358 381
4. H. van de Waterbeemd, and E. Gifford ADMET in silico modelling: towards prediction paradise? Nat. Rev. Drug Discov. 2 2003 192 204 (Pubitemid 37361664)
5. P.D. Dobson 'Metabolite-likeness' as a criterion in the design and selection of pharmaceutical drug libraries Drug Discov. Today 14 2009 31 40
6. C.A. Lipinski Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Deliv. Rev. 46 2001 3 26 (Pubitemid 33653411)
7. D. Lagorce FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects BMC Bioinformatics 9 2008 396
8. D. Lagorce The FAF-Drugs2 server: a multistep engine to prepare electronic chemical compound collections Bioinformatics 27 2011 2018 2020
9. N. Bhogal Toxicity testing: creating a revolution based on new technologies Trends Biotechnol. 23 2005 299 307 (Pubitemid 40726271)
10. A. Vedani, and M. Smiesko In silico toxicology in drug discovery - concepts based on three-dimensional models Altern. Lab. Anim. 37 2009 477 496
11. M.J. de Groot A three-dimensional protein model for human cytochrome P450 2D6 based on the crystal structures of P450 101, P450 102, and P450 108 Chem. Res. Toxicol. 9 1996 1079 1091 (Pubitemid 26347960)
12. S. Ekins Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites Drug Metab. Dispos. 29 2001 936 944 (Pubitemid 32605906)
13. F. Stoll Utility of protein structures in overcoming ADMET-related issues of drug-like compounds Drug Discov. Today 16 2011 530 538
14. H. Sun, and D.O. Scott Structure-based drug metabolism predictions for drug design Chem. Biol. Drug Des. 75 2010 3 17
15. I.V. Tetko Can we estimate the accuracy of ADME-Tox predictions? Drug Discov. Today 11 2006 700 707 (Pubitemid 44038632)
16. C.N. Cavasotto, and N. Singh Docking and high throughput docking: successes and the challenge of protein flexibility Curr. Comput. Aid. Drug Des. 4 2008 221 234
17. O. Sperandio How to choose relevant multiple receptor conformations for virtual screening: a test case of Cdk2 and normal mode analysis Eur. Biophys. J. 39 2010 1365 1372
18. A. Isvoran Exploring NMR ensembles of calcium binding proteins: perspectives to design inhibitors of protein-protein interactions BMC Struct. Biol. 11 2011 24
19. P. Bojarova, and S.J. Williams Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination Curr. Opin Chem. Biol. 12 2008 573 581
20. T. Shimada Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons Drug Metab. Pharmacokinet. 21 2006 257 276
21. C. Bode The nasty surprise of a complex drug-drug interaction Drug Discov. Today 15 2010 391 395
22. U.S. Department of Health and Human Services, F.D.A. Guidance for Industry, Drug Metabolism/Drug Interaction Studies in the Drug Development Process: Studies In Vitro 1999 http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm072104.pdf
23. F.P. Guengerich Cytochrome p450 and chemical toxicology Chem. Res. Toxicol. 21 2008 70 83 (Pubitemid 351219709)
24. S.E. Clark, and B.C. Jones Human cytochromes P450 and their role in metabolism-based drug-drug interactions A.D. Rodrigues, Drug-Drug Interactions 2002 Marcel Dekker 55 88
25. D. Zhou Comparison of methods for the prediction of the metabolic sites for CYP3A4-mediated metabolic reactions Drug Metab. Dispos. 34 2006 976 983 (Pubitemid 43763754)
26. G. Rossato Probing small-molecule binding to cytochrome P450 2D6 and 2C9: an in silico protocol for generating toxicity alerts ChemMedChem 5 2010 2088 2101
27. S.J. Park Improved docking, screening and selectivity prediction for small molecule nuclear receptor modulators using conformational ensembles J. Comput. Aid. Mol. Des. 24 2010 459 471
28. P. Rowland Crystal structure of human cytochrome P450 2D6 J. Biol. Chem. 281 2006 7614 7622 (Pubitemid 43847532)
29. C.A. Kemp Validation of model of cytochrome P450 2D6: an in silico tool for predicting metabolism and inhibition J. Med. Chem. 47 2004 5340 5346 (Pubitemid 39382784)
30. P.S. Bazeley Synergistic use of compound properties and docking scores in neural network modeling of CYP2D6 binding: predicting affinity and conformational sampling J. Chem. Inf. Model. 46 2006 2698 2708 (Pubitemid 46008139)
31. C. de Graaf Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking J. Med. Chem. 49 2006 2417 2430
32. R. Santos Role of water in molecular docking simulations of cytochrome P450 2D6 J. Chem. Inf. Model. 50 2010 146 154
33. J. Hritz Impact of plasticity and flexibility on docking results for cytochrome P450 2D6: a combined approach of molecular dynamics and ligand docking J. Med. Chem. 51 2008 7469 7477
34. R.J. Unwalla Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism J. Comput. Aid. Mol. Des. 24 2010 237 256
35. R. Shi Exploration of the binding of proton pump inhibitors to human P450 2C9 based on docking and molecular dynamics simulation J. Mol. Model. 17 2011 1941 1951
36. E. Stjernschantz, and C. Oostenbrink Improved ligand-protein binding affinity predictions using multiple binding modes Biophys. J. 98 2010 2682 2691
37. A. Kontijevskis Generalized proteochemometric model of multiple cytochrome p450 enzymes and their inhibitors J. Chem. Inf. Model. 48 2008 1840 1850
38. G. Cruciani MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist J. Med. Chem. 48 2005 6970 6979 (Pubitemid 41533118)
39. A.K. Daly Pharmacogenetics of the major polymorphic metabolizing enzymes Fundam. Clin. Pharmacol. 17 2003 27 41 (Pubitemid 36241451)
40. J.A. Williams Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios Drug Metab. Dispos. 32 2004 1201 1208 (Pubitemid 39410902)
41. P.A. Smith Towards integrated ADME prediction: past, present and future directions for modelling metabolism by UDP-glucuronosyltransferases J. Mol. Graph Model. 22 2004 507 517 (Pubitemid 38746576)
42. L. Cucurull-Sanchez Successful identification of key chemical structure modifications that lead to improved ADME profiles J. Comput. Aid. Mol. Des. 24 2010 449 458
43. M.J. Miley Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7 J. Mol. Biol. 369 2007 498 511 (Pubitemid 46678060)
44. H. Shao Crystal structures of a multifunctional triterpene/flavonoid glycosyltransferase from Medicago truncatula Plant Cell 17 2005 3141 3154
45. B. Wu Three-dimensional quantitative structure-activity relationship studies on UGT1A9-mediated 3-O-glucuronidation of natural flavonols using a pharmacophore-based comparative molecular field analysis model J. Pharmacol. Exp. Ther. 336 2011 403 413
46. M.D. Krasowski Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR Mol. Cell. Endocrinol. 334 2011 39 48
47. U. Savas Molecular mechanisms of cytochrome P-450 induction by xenobiotics: an expanded role for nuclear hormone receptors Mol. Pharmacol. 56 1999 851 857
48. C.H. Ngan The structural basis of pregnane X receptor binding promiscuity Biochemistry 48 2009 11572 11581
49. S. Ekins Challenges predicting ligand-receptor interactions of promiscuous proteins: the nuclear receptor PXR PLoS Comput. Biol. 5 2009 e1000594
50. Y.H. Liu Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study Xenobiotica 41 2011 259 280
51. M. Baes A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements Mol. Cell. Biol. 14 1994 1544 1552 (Pubitemid 24074550)
52. R.X. Xu A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer Mol. Cell 16 2004 919 928 (Pubitemid 40018402)
53. B. Windshugel Molecular dynamics simulations of the human CAR ligand-binding domain: deciphering the molecular basis for constitutive activity J. Mol. Model. 11 2005 69 79 (Pubitemid 40347925)
54. J. Küblbeck Discovery of substituted sulfonamides and thiazolidin-4-one derivatives as agonists of human constitutive androstane receptor Biochem. Pharmacol. 76 2008 1288 1297
55. J.G. DeKeyser Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane x receptor Toxicol. Sci. 120 2011 381 391
56. A. Vedani Combining protein modeling and 6D-QSAR. Simulating the binding of structurally diverse ligands to the estrogen receptor J. Med. Chem. 48 2005 3700 3703 (Pubitemid 40776845)
57. M.A. Lill Impact of induced fit on ligand binding to the androgen receptor: a multidimensional QSAR study to predict endocrine-disrupting effects of environmental chemicals J. Med. Chem. 48 2005 5666 5674 (Pubitemid 41298341)
58. W.H. Bisson Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs Proc. Natl. Acad. Sci. U. S. A. 104 2007 11927 11932 (Pubitemid 47185607)
59. D.C. Carter, and J.X. Ho Structure of serum albumin Adv. Protein Chem. 45 1994 153 203 (Pubitemid 24139888)
60. X.M. He, and D.C. Carter Atomic structure and chemistry of human serum albumin Nature 358 1992 209 215
61. J. Ghuman Structural basis of the drug-binding specificity of human serum albumin J. Mol. Biol. 353 2005 38 52 (Pubitemid 41338838)
62. M. Otagiri A molecular functional study on the interactions of drugs with plasma proteins Drug Metab. Pharmacokinet. 20 2005 309 323
63. G.S. Sheppard Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding J. Med. Chem. 49 2006 3832 3849 (Pubitemid 43967881)
64. M.D. Wendt Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2 family proteins with chemopotentiation activity in vitro and in vivo J. Med. Chem. 49 2006 1165 1181 (Pubitemid 43221663)
65. A. Varshney Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding PLoS ONE 6 2011 e17230
66. H. Liu Binding modes of flavones to human serum albumin: insights from experimental and computational studies J. Phys. Chem. B 114 2010 12938 12947
67. M. Salvalaglio Determination of energies and sites of binding of PFOA and PFOS to human serum albumin J. Phys. Chem. B 114 2010 14860 14874
68. O. Deeb Exploration of human serum albumin binding sites by docking and molecular dynamics flexible ligand-protein interactions Biopolymers 93 2010 161 170
69. F. Zsila Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking Bioinformatics 27 2011 1806 1813
70. K. Nishi Structural insights into differences in drug-binding selectivity between two forms of human alpha1-acid glycoprotein genetic variants, the A and F1*S forms J. Biol. Chem. 286 2011 14427 14434
71. F. Herve Ligand specificity of the genetic variants of human alpha1-acid glycoprotein: generation of a three-dimensional quantitative structure-activity relationship model for drug binding to the A variant Mol. Pharmacol. 54 1998 129 138 (Pubitemid 28337595)
72. V. Kopecky Jr. Structure of human alpha1-acid glycoprotein and its high-affinity binding site Biochem. Biophys. Res. Commun. 300 2003 41 46 (Pubitemid 36042927)
73. D.L. Schonfeld The 1.8- crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin J. Mol. Biol. 384 2008 393 405
74. European Medecines Agency. ICH S7B - The nonclinical Evaluation of the Poetential for delayed Ventricular Repolarisation (QT interval prolongation) by human pharmaceutics. CPMP/ICH/423/02 November 2005, http://www.emea.europa.eu/ docs/en-GB/document-library/Scientific-guideline/2009/09/WC500002841.pdf
75. R. Tabrizchi Molecular mechanisms of adverse drug reactions in cardiac tissue Handb. Exp. Pharmacol. 196 2010 77 109
76. R. Netzer Critical appraisal of available models for the detection of proarrhythmic side-effects of compounds J.G. Papp, Atrial Fibrillation: New Therapeutic Concepts 2003 IOS Press pp. 103-114
77. A.M. Aronov Predictive in silico modeling for hERG channel blockers Drug Discov. Today 10 2005 149 155 (Pubitemid 40247813)
78. J.S. Mitcheson A structural basis for drug-induced long QT syndrome Proc. Natl Acad. Sci. U. S. A. 97 2000 12329 12333
79. + channel. A model for bad behavior J. Med. Chem. 46 2003 2017 2022 (Pubitemid 36583481)
80. + channel using docking and molecular dynamics methods FEBS Lett. 579 2005 2939 2944 (Pubitemid 40725270)
81. + current J. Physiol. Sci. 58 2008 459 470
82. D. Fernandez Physicochemical features of the HERG channel drug binding site J. Biol. Chem. 279 2004 10120 10127 (Pubitemid 38372616)
83. P.J. Stansfeld Drug block of the hERG potassium channel: insight from modeling Proteins 68 2007 568 580 (Pubitemid 46981949)
84. S. Durdagi Combined receptor and ligand-based approach to the universal pharmacophore model development for studies of drug blockade to the hERG1 pore domain J. Chem. Inf. Model. 51 2011 463 474
85. O. Taboureau, and F.S. Jørgensen In silico predictions of hERG channel blockers in drug discovery: from ligand-based and target-based approaches to systems chemical biology Comb. Chem. High Throughput Screen. 14 2011 375 387
86. C. Obiol-Pardo A multiscale simulation system for the prediction of drug-induced cardiotoxicity J. Chem. Inf. Model. 51 2011 483 492
87. I. Pajeva, and M. Wiese Application of in silico methods to study ABC transporters involved in multidrug resistance M.A. Miteva, In Silico Lead Discovery 2011 Bentham Science Publishers 144 162
88. G. Williamson Interaction of positional isomers of quercetin glucuronides with the transporter ABCC2 (Cmoat, MRP2) Drug Metab. Dispos. 35 2007 1262 1268 (Pubitemid 47121765)
89. C.F. Higgins, and K.J. Linton The ATP switch model for ABC transporters Nat. Struct. Mol. Biol. 11 2004 918 926 (Pubitemid 39315294)
90. A.R. Safa Identification and characterization of the binding sites of P-glycoprotein for multidrug resistance-related drugs and modulators Curr. Med. Chem. Anticancer Agents 4 2004 1 17 (Pubitemid 38081746)
91. M. Seigneuret, and A. Garnier-Suillerot A structural model for the open conformation of the mdr1 P-glycoprotein based on the MsbA crystal structure J. Biol. Chem. 278 2003 30115 30124 (Pubitemid 36962404)
92. M.L. O'Mara, and D.P. Tieleman P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK FEBS Lett. 581 2007 4217 4222 (Pubitemid 47301854)
93. J.P. Becker Molecular models of human P-glycoprotein in two different catalytic states BMC Struct. Biol. 9 2009 3
94. S.G. Aller Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding Science 323 2009 1718 1722
95. I.K. Pajeva Comparison of the inward- and outward-open homology models and ligand binding of human P-glycoprotein FEBS J. 276 2009 7016 7026
96. F. Klepsch Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein PLoS Comput. Biol. 7 2011 e1002036
97. A.H. Dantzig Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities J. Pharmacol. Exp. Ther. 290 1999 854 862 (Pubitemid 29344586)
98. M. Achira Comparative studies to determine the selective inhibitors for P-glycoprotein and cytochrome P4503A4 AAPS Pharm. Sci. 1 1999 E18
99. A. Allali-Hassani Structural and chemical profiling of the human cytosolic sulfotransferases PLoS Biol. 5 2007 e97
100. E. Stjernschantz Comparison of murine and human estrogen sulfotransferase inhibition in vitro and in silico - implications for differences in activity, subunit dimerization and substrate inhibition Mol. Cell. Endocrinol. 317 2010 127 140
101. V. Campagna-Slater, and M. Schapira Evaluation of virtual screening as a tool for chemical genetic applications J. Chem. Inf. Model. 49 2009 2082 2091
102. B.R. Brooks CHARMM: a program for macromolecular energy, minimization, and dynamics calculations J. Comput. Chem. 4 1983 187 217
103. O. Trott, and A.J. Olson AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading J. Comput. Chem. 31 2010 455 461
104. J. Achenbach Computational tools for polypharmacology and repurposing Future Med. Chem. 3 2011 961 968
105. Y. Ito Analysis of CYP2D6 substrate interactions by computational methods J. Mol. Graph Model. 26 2008 947 956 (Pubitemid 350298014)
106. L. Afzelius State-of-the-art tools for computational site of metabolism predictions: comparative analysis, mechanistical insights, and future applications Drug Metab. Rev. 39 2007 61 86
107. J. Michel, and J.W. Essex Hit identification and binding mode predictions by rigorous free energy simulations J. Med. Chem. 51 2008 6654 6664
108. R. Abagyan, and I. Kufareva The flexible pocketome engine for structural chemogenomics E. Jacoby, Chemogenomics, Methods in Molecular Biology Vol. 575 2009 Springer 249 279
109. M.J. de Groot Novel approach to predicting P450-mediated drug metabolism: development of a combined protein and pharmacophore model for CYP2D6 J. Med. Chem. 42 1999 1515 1524 (Pubitemid 29226723)
110. C.M. Bathelt QM/MM modeling of benzene hydroxylation in human cytochrome P450 2C9 J. Phys. Chem. A 112 2008 13149 13156
111. R. Lonsdale Does compound I vary significantly between isoforms of cytochrome P450? J. Am. Chem. Soc. 133 2011 15464 15474
112. G.J.P. van Westen Proteochemometric modeling as a tool to design selective compounds and for extrapolating to novel targets Med. Chem. Commun. 2 2011 16 30
113. W.H. Lee SGC - structural biology and human health: a new approach to publishing structural biology results PLoS ONE 4 2009 e7675