The current state of drug discovery and a potential role for NMR metabolomics

Journal of Medicinal Chemistry

Volumn 57, Issue 14, 2014, Pages 5860-5870

  Powers, Robert ^a  

^a UNIVERSITY OF NEBRASKA LINCOLN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NEW DRUG;

BINDING AFFINITY; CARBON NUCLEAR MAGNETIC RESONANCE; COST CONTROL; DRUG APPROVAL; DRUG DESIGN; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG INDUSTRY; DRUG MECHANISM; FOOD AND DRUG ADMINISTRATION; HEALTH CARE COST; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HIGH THROUGHPUT SCREENING; HUMAN; IN VIVO STUDY; IONIC STRENGTH; LIFE EXPECTANCY; METABOLOMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PH; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; RNA INTERFERENCE; SYSTEMS BIOLOGY;

DRUG DISCOVERY; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; METABOLOMICS; PHARMACEUTICAL PREPARATIONS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84905046901     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401803b     Document Type: Review

References (97)

1. Liu, L.; Cline, R. R.; Schondelmeyer, S. W.; Schommer, J. C. Pharmaceutical expenditures as a correlate of population health in industrialized nations Ann. Pharmacother. 2008, 42, 368-374
2. Lichtenberg, F. R. The impact of new drug launches on longevity: evidence from longitudinal, disease-level data from 52 countries, 1982-2001 Int. J. Health Care Finance Econ. 2005, 5, 47-73
3. Lakdawalla, D. N.; Sun, E. C.; Jena, A. B.; Reyes, C. M.; Goldman, D. P.; Philipson, T. J. An economic evaluation of the war on cancer J. Health Econ. 2010, 29, 333-346
4. Lichtenberg, F. R. The Expanding Pharmaceutical Arsenal in the War on Cancer; National Bureau of Economic Research: Cambridge, MA, 2004; Vol. I, Feb 2004.
5. Hoyert, D. L.; Xu, J. Deaths: Preliminary Data for 2011 Natl. Vital Stat. Rep. 2012, 61, 1-52
6. Dieffenbach, C. W.; Fauci, A. S. Thirty years of HIV and AIDS: future challenges and opportunities Ann. Intern. Med. 2011, 154, 766-771
7. Kaufman, H. W.; Blatt, A. J.; Huang, X.; Odeh, M. A.; Superko, H. R. Blood cholesterol trends 2001-2011 in the United States: analysis of 105 million patient records PLoS One 2013, 8, e63416
8. Ford, E. S.; Ajani, U. A.; Croft, J. B.; Critchley, J. A.; Labarthe, D. R.; Kottke, T. E.; Giles, W. H.; Capewell, S. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000 N. Engl. J. Med. 2007, 356, 2388-2398
9. Kostis, J. B.; Cabrera, J.; Cheng, J. Q.; Cosgrove, N. M.; Deng, Y.; Pressel, S. L.; Davis, B. R. Association between chlorthalidone treatment of systolic hypertension and long-term survival JAMA, J. Am. Med. Assoc. 2011, 306, 2588-2593
10. Armstrong, G. L.; Conn, L. A.; Pinner, R. W. Trends in infectious disease mortality in the United States during the 20th century JAMA, J. Am. Med. Assoc. 1999, 281, 61-66
11. CDC on Infectious Diseases in the United States: 1900-99. Population Dev. Rev. 1999, 25, 635-640.
12. Health Care Cost and Utilization Report: 2011; Health Care Cost Institute, Inc.: Washington, DC, 2012; pp 1-18
13. Levy, R. Costs and benefits of pharmaceuticals: the value equation for older Americans Care Manage. J. 2002, 3, 135-142
14. Cremieux, P.-Y.; Ouellette, P.; Petit, P. Do drugs reduce utilisation of other healthcare resources? Pharmacoeconomics 2007, 25, 209-221
15. Pedersen, T. R.; Kjekshus, J.; Berg, K.; Olsson, A. G.; Wilhelmsen, L.; Wedel, H.; Pyorala, K.; Miettinen, T.; Haghfelt, T.; Faergeman, O.; Thorgeirsson, G.; Jonsson, B.; Schwartz, J. S. Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study Circulation 1996, 93, 1796-1802
16. Ali, S.; Paracha, N.; Cook, S.; Giovannoni, G.; Comi, G.; Rammohan, K.; Rieckmann, P.; Sarensen, P. S.; Vermersch, P.; Greenberg, S.; Scott, D. A.; Joyeux, A. Reduction in healthcare and societal resource utilization associated with cladribine tablets in patients with relapsing-remitting multiple sclerosis: analysis of economic data from the CLARITY study Clin. Drug Invest. 2012, 32, 15-27
17. Weintraub, W. S.; Mahoney, E. M.; Lamy, A.; Culler, S.; Yuan, Y.; Caro, J.; Gabriel, S.; Yusuf, S. Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation J. Am. Coll. Cardiol. 2005, 45, 838-845
18. Scannell, J. W.; Blanckley, A.; Boldon, H.; Warrington, B. Diagnosing the decline in pharmaceutical R&D efficiency Nature Rev. Drug Discovery 2012, 11, 191-200
19. Paul, S. M.; Mytelka, D. S.; Dunwiddie, C. T.; Persinger, C. C.; Munos, B. H.; Lindborg, S. R.; Schacht, A. L. How to improve R&D productivity: the pharmaceutical industry's grand challenge Nature Rev. Drug Discovery 2010, 9, 203-214
20. Sams-Dodd, F. Target-based drug discovery: is something wrong? Drug Discovery Today 2005, 10, 139-147
21. Cuatrecasas, P. Drug discovery in jeopardy J. Clin. Invest. 2006, 116, 2837-2842
22. Ashburn, T. T.; Thor, K. B. Drug repositioning: identifying and developing new uses for existing drugs Nature Rev. Drug Discovery 2004, 3, 673-683
23. Garattini, S. Are me-too drugs justified? J. Nephrol. 1997, 10, 283-94
24. Ullman, F.; Boutellier, R. A case study of lean drug discovery: from project driven research to innovation studios and process factories Drug Discovery Today 2008, 13, 543-550
25. Kola, I.; Landis, J. Opinion: Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Discovery 2004, 3, 711-716
26. Dickson, M.; Gagnon, J. P. Key factors in the rising cost of new drug discovery and development Nature Rev. Drug Discovery 2004, 3, 417-429
27. Miller, G. Is Pharma running out of brainy ideas? Science 2010, 329, 502-504
28. Livermore, D. Can better prescribing turn the tide of resistance? Nature Rev. Microbiol. 2004, 2, 73-78
29. Hendrie, C. A. The funding crisis in psychopharmacology: an historical perspective J. Psychopharmacol. 2010, 24, 439-440
30. Nierenberg, A. A. The perfect storm: CNS drug development in trouble CNS Spectrums 2010, 15, 282-283
31. Offit, P. A. Why Are Pharmaceutical Companies Gradually Abandoning Vaccines? Health Affairs 2005, 24, 622-630
32. Garber, A. M. Perspective: an uncertain future for cardiovascular drug development? N. Engl. J. Med. 2009, 360, 1169-1171
33. Booth, B.; Zemmel, R. Opinion: Quest for the best Nature Rev. Drug Discovery 2003, 2, 838-841
34. Wermuth, C. G. Similarity in drugs: reflections on analogue design Drug Discovery Today 2006, 11, 348-354
35. Seidelmann, O. Outsourcing of chemical research: promising field for service providers Chim. Oggi 2004, 18-21
36. Cavalla, D. The extended pharmaceutical enterprise Drug Discovery Today 2003, 8, 267-274
37. Ullman, F.; Boutellier, R. Drug discovery: are productivity metrics inhibiting motivation and creativity? Drug Discovery Today 2008, 13, 997-1001
38. Mackay, M.; Street, S. D. A.; McCall, J. M. Risk reduction in drug discovery and development Curr. Top. Med. Chem. (Sharjah, United Arab Emirates) 2005, 5, 1087-1090
39. Handen, J. S. The industrialization of drug discovery Drug Discovery Today 2002, 7, 83-85
40. Schmid, E. F.; Smith, D. A. Is pharmaceutical R&D just a game of chance or can strategy make a difference? Drug Discovery Today 2004, 9, 18-26
41. Mayr, L. M.; Fuerst, P. The future of high-throughput screening J. Biomol. Screening 2008, 13, 443-448
42. Szymanski, P.; Markowicz, M.; Mikiciuk-Olasik, E. Adaptation of high-throughput screening in drug discovery-toxicological screening tests Int. J. Mol. Sci. 2012, 13, 427-452
43. Mayr, L. M.; Bojanic, D. Novel trends in high-throughput screening Curr. Opin. Pharmacol. 2009, 9, 580-588
44. Martis, E. A.; Radhakrishnan, R.; Badve, R. R. High-Throughput Screening: The Hits and Leads of Drug Discovery-An Overview J. Appl. Pharm. Sci. 2011, 1, 2-10
45. Lahana, R. How many leads from HTS? Drug Discovery Today 1999, 4, 447-448
46. Macarron, R.; Banks, M. N.; Bojanic, D.; Burns, D. J.; Cirovic, D. A.; Garyantes, T.; Green, D. V. S.; Hertzberg, R. P.; Janzen, W. P.; Paslay, J. W.; Schopfer, U.; Sittampalam, G. S. Impact of high-throughput screening in biomedical research Nature Rev. Drug Discovery 2011, 10, 188-195
47. Dove, A. Screening for content-the evolution of high throughput Nature Biotechnol. 2003, 21, 859-864
48. Kubinyi, H. Opinion: Drug research: myths, hype and reality Nature Rev. Drug Discovery 2003, 2, 665-668
49. Seidler, J.; McGovern, S. L.; Doman, T. N.; Shoichet, B. K. Identification and prediction of promiscuous aggregating inhibitors among known drugs J. Med. Chem. 2003, 46, 4477-4486
50. Rishton, G. M. Reactive compounds and in vitro false positives in HTS Drug Discovery Today 1997, 2, 382-384
51. McGovern, S. L.; Caselli, E.; Grigorieff, N.; Shoichet, B. K. A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening J. Med. Chem. 2002, 45, 1712-1722
52. McGovern, S. L.; Helfand, B. T.; Feng, B.; Shoichet, B. K. A Specific Mechanism of Nonspecific Inhibition J. Med. Chem. 2003, 46, 4265-4272
53. Malo, N.; Hanley, J. A.; Cerquozzi, S.; Pelletier, J.; Nadon, R. Statistical practice in high-throughput screening data analysis Nature Biotechnol. 2006, 24, 167-175
54. Shoichet, B. K. Interpreting Steep Dose-Response Curves in Early Inhibitor Discovery J. Med. Chem. 2006, 49, 7274-7277
55. Snowden, M. A.; Green, D. V. S. The impact of diversity-based, high-throughput screening on drug discovery: "chance favours the prepared mind" Curr. Opin. Drug Discovery Dev. 2008, 11, 553-558
56. Djuric, S. W.; Akritopoulou-Zanze, I.; Cox, P. B.; Galasinski, S. Compound collection enhancement and paradigms for high-throughput screening-an update Annu. Rep. Med. Chem. 2010, 45, 409-428
57. Petrone, P. M.; Wassermann, A. M.; Lounkine, E.; Kutchukian, P.; Simms, B.; Jenkins, J.; Selzer, P.; Glick, M. Biodiversity of small molecules-a new perspective in screening set selection Drug Discovery Today 2013, 18, 674-680
58. Harper, G.; Pickett, S. D.; Green, D. V. S. Design of a compound screening collection for use in high throughput screening Comb. Chem. High Throughput Screening 2004, 7, 63-71
59. Bajorath, J. Integration of virtual and high-throughput screening Nature Rev. Drug Discovery 2002, 1, 882-894
60. Anderson, A. C. The Process of Structure-Based Drug Design Chem. Biol. 2003, 10, 787-797
61. Ramstrom, O.; Lehn, J.-M. Drug discovery by dynamic combinatorial libraries Nature Rev. Drug Discovery 2002, 1, 26-36
62. Erlanson, D. A.; McDowell, R. S.; O'Brien, T. Fragment-Based Drug Discovery J. Med. Chem. 2004, 47, 3463-3482
63. Nicholson, J. K.; Connelly, J.; Lindon, J. C.; Holmes, E. Innovation: Metabonomics: a platform for studying drug toxicity and gene function Nature Rev. Drug Discovery 2002, 1, 153-161
64. Fiehn, O. Metabolomics-the link between genotypes and phenotypes Plant Mol. Biol. 2002, 48, 155-171
65. Guo, Y.; Xiao, P.; Lei, S.; Deng, F.; Xiao, G. G.; Liu, Y.; Chen, X.; Li, L.; Wu, S.; Chen, Y.; Hui, J.; Tan, L.; Xie, J.; Zhu, X.; Liang, S.; Deng, H. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes Acta Biochim. Biophys. Sin. 2008, 40, 426-436
66. Nicholson, J. K.; Lindon, J. C.; Holmes, E. "Metabonomics": understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data Xenobiotica 1999, 29, 1181-1189
67. Zhang, B.; Powers, R. Using NMR-based metabolomics to study the regulation of biofilm formation Future Med. Chem. 2012, 4, 1273-1306
68. Gebregiworgis, T.; Powers, R. Application of NMR Metabolomics to Search for Human Disease Biomarkers Comb. Chem. High Throughput Screening 2012, 15, 595-610
69. Powers, R. NMR metabolomics and drug discovery Magn. Reson. Chem. 2009, 47, S2-S11
70. Bollard, M. E.; Stanley, E. G.; Lindon, J. C.; Nicholson, J. K.; Holmes, E. NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition NMR Biomed. 2005, 18, 143-162
71. Coen, M.; Holmes, E.; Lindon, J. C.; Nicholson, J. K. NMR-Based Metabolic Profiling and Metabonomic Approaches to Problems in Molecular Toxicology Chem. Res. Toxicol. 2008, 21, 9-27
72. Dunn, W. B.; Broadhurst, D. I.; Atherton, H. J.; Goodacre, R.; Griffin, J. L. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy Chem. Soc. Rev. 2011, 40, 387-426
73. Griffin, J. L. Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids and tissues for characterisation of xenobiotic toxicity and disease diagnosis Curr. Opin. Chem. Biol. 2003, 7, 648-654
74. Reo, N. V. NMR-based metabolomics Drug Chem. Toxicol. 2002, 25, 375-382
75. 1H-NMR-based metabolomics Expert Rev. Mol. Diagn. 2006, 6, 717-731
76. Wishart, D. S. Quantitative metabolomics using NMR TrAC, Trends Anal. Chem. 2008, 27, 228-237
77. Lei, S.; Powers, R. NMR Metabolomics Analysis of Parkinson's Disease Curr. Metabolomics 2013, 1, 191-209
78. Zhang, B.; Halouska, S.; Gaupp, R.; Lei, S.; Snell, E.; Fenton, R. J.; Barletta, R. G.; Somerville, G. A.; Powers, R. Revisiting Protocols for the NMR Analysis of Bacterial Metabolomes J. Integr. OMICS 2013, 2, 120-137
79. Broadhurst, D. I.; Kell, D. B. Statistical strategies for avoiding false discoveries in metabolomics and related experiments Metabolomics 2006, 2, 171-196
80. Worley, B.; Powers, R. Multivariate analysis in metabolomics Curr. Metabolomics 2013, 1, 92-107
81. van den Berg, R. A.; Hoefsloot, H. C.; Westerhuis, J. A.; Smilde, A. K.; van der Werf, M. J. Centering, scaling, and transformations: improving the biological information content of metabolomics data BMC Genomics 2006, 7, 142
82. Craig, A.; Cloareo, O.; Holmes, E.; Nicholson, J. K.; Lindon, J. C. Scaling and normalization effects in NMR spectroscopic metabonomic data sets Anal. Chem. 2006, 78, 2262-2267
83. Kjeldahl, K.; Bro, R. Some common misunderstandings in chemometrics J. Chemom. 2010, 24, 558-564
84. Worley, B.; Halouska, S.; Powers, R. Utilities for quantifying separation in PCA/PLS-DA scores plots Anal. Biochem. 2013, 433, 102-104
85. Werth, M. T.; Halouska, S.; Shortridge, M. D.; Zhang, B.; Powers, R. Analysis of Metabolomic PCA Data using Tree Diagrams Anal. Biochem. 2010, 399, 56-63
86. Sansone, S.-A.; Fan, T.; Goodacre, R.; Griffin, J. L.; Hardy, N. W.; Kaddurah-Daouk, R.; Kristal, B. S.; Lindon, J.; Mendes, P.; Morrison, N.; Nikolau, B.; Robertson, D.; Sumner, L. W.; Taylor, C.; van, d. W. M.; van, O. B.; Fiehn, O. The Metabolomics Standards Initiative Nature Biotechnol. 2007, 25, 846-848
87. Salek, R. M.; Haug, K.; Steinbeck, C. Dissemination of metabolomics results: role of MetaboLights and COSMOS Gigascience 2013, 2, 8
88. Canelas, A.; Ras, C.; ten Pierick, A.; van Dam, J.; Heijnen, J.; van Gulik, W. Leakage-free rapid quenching technique for yeast metabolomics Metabolomics 2008, 4, 226-239
89. Blaise, B. J. Data-Driven Sample Size Determination for Metabolic Phenotyping Studies Anal. Chem. 2013, 85, 8943-8950
90. Halouska, S.; Powers, R. Negative impact of noise on the principal component analysis of NMR data J. Magn. Reson. 2006, 178, 88-95
91. Worley, B.; Powers, R. MVAPACK: A Complete Data Handling Package for NMR Metabolomics ACS Chem. Biol. 2014, accepted for publication.
92. Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution Drug Discovery Today: Technol. 2004, 1, 337-341
93. Gribbon, P.; Sewing, A. High-throughput drug discovery: what can we expect from HTS? Drug Discovery Today 2005, 10, 17-22
94. Schuster, D.; Laggner, C.; Langer, T. Why drugs fail-a study on side effects in new chemical entities Curr. Pharm. Des. 2005, 11, 3545-3559
95. Forgue, P.; Halouska, S.; Werth, M.; Xu, K.; Harris, S.; Powers, R. NMR Metabolic Profiling of Aspergillus nidulans to Monitor Drug and Protein Activity J. Proteome Res. 2006, 5, 1916-1923
96. Halouska, S.; Chacon, O.; Fenton, R. J.; Zinniel, D. K.; Barletta, R. G.; Powers, R. Use of NMR Metabolomics To Analyze the Targets of d -Cycloserine in Mycobacteria: Role of d -Alanine Racemase J. Proteome Res. 2007, 6, 4608-4614
97. Halouska, S.; Fenton, R. J.; Barletta, R. G.; Powers, R. Predicting the in Vivo Mechanism of Action for Drug Leads Using NMR Metabolomics ACS Chem. Biol. 2012, 7, 166-171