Systems pharmacology: Network analysis to identify multiscale mechanisms of drug action

Annual Review of Pharmacology and Toxicology

Volumn 52, Issue , 2012, Pages 505-521

  Zhao, Shan ^a   Iyengar, Ravi ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Adverse event predictions; Drug discovery; Enhanced pharmacodynamics; Genomics and personalized therapy

Indexed keywords

ABACAVIR; ATORVASTATIN; AZATHIOPRINE; CAPECITABINE; CARBAMAZEPINE; CETUXIMAB; CLOPIDOGREL; CLOZAPINE; CODEINE; DASATINIB; ERLOTINIB; GEFITINIB; HALOPERIDOL; IMATINIB; IRINOTECAN; METHOTREXATE; NORTRIPTYLINE; PANITUMUMAB; PROMAZINE; QUETIAPINE; RASBURICASE; RETINOIC ACID; RISPERIDONE; SUNITINIB; TRASTUZUMAB; VALPROIC ACID; WARFARIN; ZIPRASIDONE;

ADVERSE OUTCOME; ARTICLE; BLEEDING; COLORECTAL CANCER; DNA POLYMORPHISM; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG RESEARCH; DRUG STRUCTURE; DRUG TARGETING; GASTROINTESTINAL STROMAL TUMOR; GENOMICS; HUMAN; LUNG NON SMALL CELL CANCER; METABOLOMICS; NETWORK LEARNING; PHARMACOGENOMICS; PHARMACOLOGY; PRIORITY JOURNAL; PROTEOMICS; SYSTEMS PHARMACOLOGY; TARDIVE DYSKINESIA; THERAPY EFFECT; TREATMENT RESPONSE;

ANIMALS; DATABASES, FACTUAL; DRUG DELIVERY SYSTEMS; DRUG DISCOVERY; HUMANS; METABOLOMICS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; PROTEOMICS; SYSTEMS BIOLOGY;

EID: 84855906454     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-010611-134520     Document Type: Article

References (89)

1. Li JW-H, Vederas JC. 2009. Drug discovery and natural products: end of an era or an endless frontier? Science 325:161-65
2. Fitzgerald G. 2010. Drug development needs a new brand of science. Nature 468:869
3. Brunton LL, Chabner BA, Knollman BC, eds. 2010. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. 1808 pp. 12th ed.
4. Davidson EH. 2010. Emerging properties of animal gene regulatory networks. Nature 468:911-20
5. Stark C, Breitkreutz B-J, Chatr-Aryamontri A, Boucher L, Oughtred R, et al. 2011. The BioGRID Interaction Database: 2011 update. Nucleic Acids Res. 39:D698-704
6. Zhao S, Li S. 2010. Network-based relating pharmacological and genomic spaces for drug target identification. PLoS ONE 5:e11764
7. Barab́asi A-L, Gulbahce N, Loscalzo J. 2011. Network medicine: a network-based approach to human disease. Nat. Rev. Genet. 12:56-68
8. Vidal M, Cusick ME, Barab́asi A-L. 2011. Interactome networks and human disease. Cell 144:986-98
9. Ferrell JE, Tsai TY-C, Yang Q. 2011. Modeling the cell cycle: Why do certain circuits oscillate? Cell 144:874-85
10. Singhania R, Sramkoski RM, Jacobberger JW, Tyson JJ. 2011. A hybrid model of mammalian cell cycle regulation. PLoS Comput. Biol. 7:e1001077
11. Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, et al. 2008. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell 133:666-80 (Pubitemid 351636307)
12. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, et al. 2008. DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 36:D901-6 (Pubitemid 351149842)
13. Zhao F, Xuan Z, Liu L, Zhang MQ. 2005. TRED: a Transcriptional Regulatory Element Database and a platform for in silico gene regulation studies. Nucleic Acids Res. 33:D103-7 (Pubitemid 40207839)
14. Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barab́asi AL. 2007. The human disease network. Proc. Natl. Acad. Sci. USA 104:8685-90 (Pubitemid 47175372)
15. Berger SI, Ma'ayan A, Iyengar R. 2010. Systems pharmacology of arrhythmias. Sci. Signal. 3:ra30
16. Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, et al. 2005. Formation of regulatory patterns during signal propagation in a mammalian cellular network. Science 309:1078-83 (Pubitemid 41134466)
17. Chatr-aryamontri A, Ceol A, Peluso D, Nardozza A, Panni S, et al. 2009. VirusMINT: a viral protein interaction database. Nucleic Acids Res. 37:D669-73
18. Chautard E, Ballut L, Thierry-Mieg N, Ricard-Blum S. 2009. MatrixDB, a database focused on extracellular protein-protein and protein-carbohydrate interactions. Bioinformatics 25:690-91
19. Sharan R, Ulitsky I, Shamir R. 2007. Network-based prediction of protein function. Mol. Syst. Biol. 3:88
20. Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, et al. 2009. PID: the Pathway Interaction Database. Nucleic Acids Res. 37:D674-79
21. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Ḧortnagel K, et al. 2004. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427:537-41 (Pubitemid 38209110)
22. Aithal GP, Day CP, Kesteven PJ, Daly AK. 1999. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353:717-19 (Pubitemid 29103806)
23. Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, et al. 2010. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327:78-81
24. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, et al. 2006. The Connectivity Map: using geneexpression signatures to connect small molecules, genes, and disease. Science 313:1929-35 (Pubitemid 44497995)
25. Rix U, Remsing Rix LL, Terker AS, Fernbach NV, Hantschel O, et al. 2010. A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells. Leukemia 24:44-50
26. Muroi M, Kazami S, Noda K, Kondo H, Takayama H, et al. 2010. Application of proteomic profiling based on 2D-DIGE for classification of compounds according to the mechanism of action. Chem. Biol. 17:460-70
27. Kaddurah-Daouk R, Kristal BS, Weinshilboum RM. 2008. Metabolomics: a global biochemical approach to drug response and disease. Annu. Rev. Pharmacol. Toxicol. 48:653-83 (Pubitemid 351738167)
28. Kaddurah-Daouk R, McEvoy J, Baillie RA, Lee D, Yao JK, et al. 2007. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol. Psychiatry 12:934-45 (Pubitemid 47482696)
29. Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, et al. 2010. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomicsinformed pharmacogenomics. Clin. Pharmacol. Ther. 89:97-104
30. Evans WE, McLeod HL. 2003. Pharmacogenomics-drug disposition, drug targets, and side effects. N. Engl. J. Med. 348:538-49 (Pubitemid 36159890)
31. Drazen JM, Silverman EK, Lee TH. 2000. Heterogeneity of therapeutic responses in asthma. Br. Med. Bull. 56:1054-70 (Pubitemid 32417168)
32. Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ. 2009. Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet. Genomics 19:129-38
33. De RoockW, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, et al. 2010. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304:1812-20
34. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. 2009. Codeine, ultrarapid-metabolism genotype, and postoperative death. N. Engl. J. Med. 361:827-28
35. Daĺen P, Dahl ML, Bernal Ruiz ML, Nordin J, Bertilsson L. 1998. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin. Pharmacol. Ther. 63:444-52 (Pubitemid 28214968)
36. Beer B, Erb R, Pitterl F, Niedersẗatter H, Maro ̃ nas O, et al. 2011. CYP2D6 genotyping by liquid chromatography-electrospray ionization mass spectrometry. Anal. Bioanal. Chem. 400(8):2361-70
37. Guengerich FP. 2002. Cytochrome P450 enzymes in the generation of commercial products. Nat. Rev. Drug Discov. 1:359-66 (Pubitemid 37361465)
38. Trevi ̃ no LR, Shimasaki N, Yang W, Panetta JC, Cheng C, et al. 2009. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J. Clin. Oncol. 27:5972-78
39. van Erp NP, Eechoute K, van der Veldt AA, Haanen JB, Reyners AKL, et al. 2009. Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity. J. Clin. Oncol. 27:4406-12
40. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, et al. 2003. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 21:4342-49 (Pubitemid 46621810)
41. Kobayashi S, Boggon TJ, Dayaram T, J̈anne PA, Kocher O, et al. 2005. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352:786-92 (Pubitemid 40271173)
42. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, et al. 2005. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2:e73
43. Mallal S, Phillips E, Carosi G, Molina J-M,Workman C, et al. 2008. HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med. 358:568-79
44. Ingle JN, Schaid DJ, Goss PE, Liu M, Mushiroda T, et al. 2010. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. J. Clin. Oncol. 28:4674-82
45. KleinTE, Chang JT, ChoMK, Easton KL, Fergerson R, et al. 2001. Integrating genotype and phenotype information: an overview of thePharmGKBproject.Pharmacogenetics Research Network and Knowledge Base. Pharmacogenomics J. 1:167-70
46. AbrahamAK, Maurer TS,KalgutkarAS, GaoX,LiM, et al. 2011. Pharmacodynamicmodel of parathyroid hormonemodulation by a negative allosteric modulator of the calcium-sensing receptor. AAPS J. 13:265-73
47. Bhalla US, Iyengar R. 1999. Emergent properties of networks of biological signaling pathways. Science 283:381-87
48. Tanaka K, Augustine GJ. 2008. A positive feedback signal transduction loop determines timing of cerebellar long-term depression. Neuron 59:608-20
49. Panetta JC, Sparreboom A, Pui C-H, Relling MV, Evans WE. 2010. Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells. PLoS Comput. Biol. 6:e1001019
50. Dijkstra EW. 1959. A note on two problems in connexion with graphs. Numer. Math. 1:269-71
51. Huang T, Wang P, Ye Z-Q, Xu H, He Z, et al. 2010. Prediction of deleterious non-synonymous SNPs based on protein interaction network and hybrid properties. PLoS ONE 5:e11900
52. Kanehisa M, Goto S, FurumichiM,TanabeM,HirakawaM. 2010.KEGGfor representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38:D355-60
53. AshburnerM, Ball CA, Blake JA, Botstein D, Butler H, et al. 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25:25-29 (Pubitemid 30257031)
54. Matthews L, Gopinath G, Gillespie M, Caudy M, Croft D, et al. 2009. Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 37:D619-22
55. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, et al. 2010. NetPath: a public resource of curated signal transduction pathways. Genome Biol. 11:R3
56. Holly TA, Drincic A, Byun Y, Nakamura S, Harris K, et al. 1999. Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo. J. Mol. Cell. Cardiol. 31:1709-15 (Pubitemid 29414590)
57. Schaller S, Paradis S, Ngoh GA, Assaly R, Buisson B, et al. 2010. TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J. Pharmacol. Exp. Ther. 333:696-706
58. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. 2004. Stromal cell-derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300-5 (Pubitemid 39557491)
59. Diedrich M, Tadic J, Mao L, Wacker MA, Nebrich G, et al. 2007. Heart protein expression related to age and sex in mice and humans. Int. J. Mol. Med. 20:865-74
60. Morange PE, Saut N, Alessi MC, Yudkin JS, Margaglione M, et al. 2007. Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters: the HIFMECH study. Arterioscler. Thromb. Vasc. Biol. 27:2250-57 (Pubitemid 350287257)
61. Shintani S,Murohara T, Ikeda H, Ueno T, Honma T, et al. 2001. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776-79 (Pubitemid 32550062)
62. Mukherjee D, Nissen SE, Topol EJ. 2011. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286:954-59
63. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, et al. 2004. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937-52 (Pubitemid 39208455)
64. Nissen SE, Wolski K. 2007. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356:2457-71 (Pubitemid 46919772)
65. Caroff SN, Hurford I, Lybrand J, Campbell EC. 2011. Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial. Neurol. Clin. 29:127-48
66. Saltz BL, Woerner MG, Kane JM, Lieberman JA, Alvir JM, et al. 1991. Prospective study of tardive dyskinesia incidence in the elderly. JAMA 266:2402-6
67. Schmidtke P, Le Guilloux V, Maupetit J, Tuff́ery P. 2010. Fpocket: online tools for protein ensemble pocket detection and tracking. Nucleic Acids Res. 38(Suppl.):W582-89
68. Ballester PJ, Mitchell JBO. 2010. A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking. Bioinformatics 26:1169-75
69. Thangudu RR, Tyagi M, Shoemaker BA, Bryant SH, Panchenko AR, Madej T. 2010. Knowledge-based annotation of small molecule binding sites in proteins. BMC Bioinformatics 11:365
70. Chang RL, Xie L, Xie L, Bourne PE, Palsson BØ. 2010. Drug off-target effects predicted using structural analysis in the context of a metabolic network model. PLoS Comput. Biol. 6:e1000938
71. Kitchen DB, Decornez H, Furr JR, Bajorath J. 2004. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug Discov. 3:935-49 (Pubitemid 39529931)
72. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. 2007. Relating protein pharmacology by ligand chemistry. Nat. Biotechnol. 25:197-206 (Pubitemid 46227119)
73. Schneider G, Fechner U. 2005. Computer-based de novo design of drug-like molecules. Nat. Rev. Drug Discov. 4:649-63 (Pubitemid 41149759)
74. Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, et al. 2011. Impact of high-throughput screening in biomedical research. Nat. Rev. Drug Discov. 10:188-95
75. Gleeson MP, Hersey A, Montanari D, Overington J. 2011. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat. Rev. Drug Discov. 10:197-208
76. Wilson ID. 2011. High-performance liquid chromatography-mass spectrometry (HPLC-MS)-based drug metabolite profiling. Methods Mol. Biol. 708:173-90
77. Lenz EM. 2011. Metabolic profiling. Methods Mol. Biol. 708:299-319
78. Clemons PA, Bodycombe NE, Carrinski HA, Wilson JA, Shamji AF, et al. 2010. Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles. Proc. Natl. Acad. Sci. USA 107:18787-92
79. Iskar M, CampillosM, KuhnM, Jensen LJ, vanNoort V, Bork P. 2010. Drug-induced regulation of target expression. PLoS Comput. Biol. 6:e1000925
80. Kim KA, Park PW, Hong SJ, Park J-Y. 2008. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin. Pharmacol. Ther. 84:236-42
81. Wadelius M, S̈orlin K, Wallerman O, Karlsson J, Yue Q-Y, et al. 2004. Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J. 4:40-48 (Pubitemid 38256604)
82. Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, Ishitsuka H. 1998. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res. 58:685-90 (Pubitemid 28099478)
83. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, et al. 2008. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26:1626-34
84. Debiec-RychterM,Dumez H, Judson I, WasagB,Verweij J, et al. 2004. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer 40:689-95 (Pubitemid 38326618)
85. Kakizuka A, MillerWH, Umesono K, Warrell RP, Frankel SR, et al. 1991. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARαwith a novel putative transcription factor, PML. Cell 66:663-74 (Pubitemid 121001702)
86. Chung W-H, Hung S-I, Hong H-S, Hsih M-S, Yang L-C, et al. 2004. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428:486 (Pubitemid 38480527)
87. Mallal S, Nolan D, Witt C, MaselG,Martin A, et al. 2002. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359:727-32 (Pubitemid 34215071)
88. Warne T, Moukhametzianov R, Baker JG, Nehḿe R, Edwards PC, et al. 2011. The structural basis for agonist and partial agonist action on a β1-adrenergic receptor. Nature 469:241-44
89. Erlanson DA, Arndt JW, Cancilla MT, Cao K, Elling RA, et al. 2011. Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery. Bioorg. Med. Chem. Lett. 21:3083-78