Medicinal chemistry for 2020

Future Medicinal Chemistry

Volumn 3, Issue 14, 2011, Pages 1765-1786

  Satyanarayanajois, Seetharama D ^a   Hill, Ronald A ^a  

^a UNIVERSITY OF LOUISIANA AT MONROE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARIPIPRAZOLE; BRENTUXIMAB VEDOTIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EUROPIUM; MAYTANSINE; PEPTIDOMIMETIC AGENT; PIOGLITAZONE; PROTEIN BCL 2; PROTEIN MCL 1; PROTEIN MDM2; PROTEIN P53; TRASTUZUMAB; TROGLITAZONE; VARENICLINE;

BIODIVERSITY; CHEMISTRY; CLUSTER ANALYSIS; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG EFFICACY; DRUG MARKETING; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG TRANSFORMATION; HUMAN; MEDICINAL CHEMISTRY; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; SURFACE PLASMON RESONANCE;

CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; MOLECULAR MIMICRY; PEPTIDES; PHARMACOLOGY; PROTEIN BINDING;

EID: 80054906857     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.11.135     Document Type: Review

References (147)

1. Proudfoot JR. Drug likeness and analogue-based drug discovery. In: Analogue-Based Drug Discovery. IUPAC. Fischer J, Ganellin CR (Eds). Wiley-VCH, Germany (2006).
2. Wang J, Hou T. Drug and drug candidate building block analysis. J. Chem. Inf. Model. 50(1), 55-67 (2010).
3. Nader F, Paul G, Robert G Jr. Lead generation: reality check on commonly held views. Exp. Opin. Drug Discov. 3(7), 733-744 (2008).
4. Chene P. Drugs targeting protein-protein interactions. Chem. Med. Chem. 1(4), 400-411 (2006).
5. Sperandio O, Reynes CH, Camproux AC, Villoutreix BO. Rationalizing the chemical space of protein-protein interaction inhibitors. Drug Discov. Today 15(5), 220-229 (2010).
6. Stumpf MP, Thorne T, de Silva E et al. Estimating the size of human interactome. Proc. Natl Acad Sci. USA 105(19), 6959-6964 (2008).
7. Drug development cost estimates hard to swallow. News. CMAJ 180(3), 279-280 (2009).
8. Light DW, Warburton R. Demythologizing the high costs of pharmaceutical research. BioSocieties 6, 34-50 (2011).
9. Cressey D. Pfizer slashes R & D. News in Focus. Nature 470 (7333), 154 (2011).
10. Zinzalla G, Thurston DE. Targeting protein-protein interactions for therapeutic intervention: a challenge for the future. Future Med. Chem. 1(1), 65-93 (2009).
11. Ester C, Uetz P. The FF domains of yeast U1 snRNP protein Prp40 mediate interactions with Luc7 and Snu71. BMC Biochem. 9, 29 (2008).
12. Maier RH, Maier CJ, Onder K. Construction of improved yeast two-hybrid libraries. Methods Mol. Biol. 729, 71-84 (2011).
13. McDowall MD, Scott MS, Barton GJ. PPIs: human protein-protein interaction prediction database. Nucleic Acid Res. 37 D651-D656 (2008).
14. Hosur R, Xu J, Bienkowska J, Berger B. iWRAP: an interface threading approach with application to prediction of cancer-related protein-protein interactions. J. Mol. Biol. 405(5), 1295-1310 (2011).
15. Keller TH, Pichota A, Yin Z. A practical view of druggability. Curr. Opin. Chem. Biol. 10(4), 357-361 (2006).
16. Fuller JC, Burgoyne NJ, Jackson RM. Predicting druggable binding sites at the protein-protein interface. Drug Discov. Today 14(3/4), 155-161 (2009).
17. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450 (7171), 1001-1009 (2007). (Pubitemid 350273630)
18. Reichmann D, Rahat O, Cohen M, Neuvirth H, Schreiber G. The molecular architecture of protein-protein binding sites. Curr. Opin. Stru. Biol. 17(1), 67-76 (2007). (Pubitemid 46240815)
19. Protein-protein complexes: analysis, modeling and drug design. Zacharias M (Ed.). Imperial College Press, London (2010).
20. Liu D, Xu R, Cowburn D. Segmental isotopic labeling of proteins for nuclear magnetic resonance. In: Methods in Enzymology (Volume 462). Muir TW (Ed.). Elsevier Inc., MC, USA 151-171 (2009).
21. Kei M, Smith JC. Coarse-grained biomolecular simulation: transferability between different protein structural classes. Biophys. J. 95(4), 1639-1648 (2008).
22. Spijker P, van Hoof B, Debertrand M, Markvoort AJ, Vaidehi N, Hilbers PAJ. Coarse grained molecular dynamics simulations of transmembrane protein-lipid systems. Int. J. Mol. Sci. 11(6), 2393-2420 (2010).
23. Maragakis P, Lindorff-Larsen K, Eastwood MP et al. Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins. J. Phys. Chem. B 112(19), 6155-6158 (2008).
24. Landgraf R. HER2 (ERBB2): functional diversity from structurally conserved building blocks. Breast Cancer Res. 9(1), 202 (2007).
25. Ferguson KM. Structure-based view of epidermal growth factor receptor regulation. Ann. Rev. Biophys. 37, 353-373 (2008).
26. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat. Rev. Cancer 9(7), 463-475 (2009).
27. Mineev KS, Bocharov EV, Pustovalova YE, Bocharova OV, Chupin VV, Arseniev AS. Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases. J. Mol. Biol. 400(2), 231-243 (2010).
28. Telesco SE, Radhakrishnan R. Atomic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study. Biophys. J. 96(6), 2321-2334 (2009).
29. Tuncbag N, Gursoy A, Keskin O. Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy. Bioinformatics 25 (12), 1513-1520 (2009).
30. Moreira IS, Fernandes PA, Ramos MJ. Hot spots - a review of the protein-protein interface determinant amino-acid residues. Proteins 68(4), 803-812 (2007). (Pubitemid 47434705)
31. Kastritis P, Moal I, Hwang H et al. A structure-based benchmark for protein-protein binding affinity. Protein Sci. 20(3), 482-491 (2011).
32. Vries SJ, Dijk MV, Bonvin AMJJ. The HADDOCK web server for data driven biomolecular docking. Nat. Protoc. 5(5), 883-897 (2010).
33. Vasker IA, Kundrotas P. Predicting 3D structure of protein-protein complexes. Curr. Pharm. Biotech. 9(2), 57-66 (2008).
34. Bai H, Yang K, Yu D, Zhang C, Chen F, Lai L. Predicting kinetic constants of protein-protein interactions based on structural properties. Proteins 79 (3), 720-734 (2011).
35. Murray JK, Gellman SH. Targeting protein-protein interactions: lessons from p53/MDM2. Biopolymers (Peptide Sci.) 88(5), 657-686 (2007). (Pubitemid 47556148)
36. Pharmers hope for first plant drug harvest. News and analysis, Nat. Rev. Drug Discov. 10(2), 81-82 (2011).
37. Leader B, Baca QJ, Golan GE. Protein therapeutics: a summary and pharmacological classification. Nat. Rev. Drug Discov. 7(1), 21-39 (2008).
38. Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat. Rev. Drug Discov. 9(10), 767-774 (2010).
39. Robert NJ, Leyland-Jones B, Asmar L. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2 overexpressing metastatic breast cancer. J. Clin. Oncol. 24(18), 2786-2792 (2006). (Pubitemid 46630577)
40. Baselga J. Treatment of HER2-overexpressing breast cancer. Ann. Oncol. 21(7), 36-40 (2010).
41. Antibody-efficacy in lymphoma. News and analysis. Nature Rev. Drug Discov. 10(2), 86 (2011).
42. Beck A, Senter P, Chari R. World antibody drug conjugate summit Europe. mAbs 3(4), 331-337 (2011).
43. Teicher BA. Antibody-drug conjugate targets. Curr. Cancer Drug Targets 9(8), 982-1004 (2009).
44. Hughes B. Antibody-drug conjugates for cancer: poised to deliver? Nat. Rev. Drug Discov. 9(9), 665-667 (2010).
45. Lanthier M, Behrman R, Nardinelli C. Economic issues with follow-on protein products. Nat. Rev. Drug Discov. 7(9), 733-737 (2008).
46. Jefferis R, LeFranc MP. Human immunoglobulin allotypes-possible implications for imminogenecity. mAbs 1(4), 332-338 (2009).
47. Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity residues in the CDR regions. mAbs 2(3), 256-265 (2010).
48. Benyamini H, Friedler A. Using peptides to study protein-protein interactions. Future Med. Chem. 2(6), 989-1003 (2010).
49. Pollaro L, Heinis C. Strategies to prolong the plasma residence time of peptide drugs. Med. Chem. Comm. 1, 319-324 (2010).
50. McGregor DP. Discovering and improving novel peptide therapeutics. Curr. Opin. Pharmacol. 8(5), 616-619 (2008).
51. Hess S, Ovadia O, Shalev DE et al. Effect of structural and conformation modifications, including backbone cyclization of hydrophilic hexapeptides on their intestinal permeability and enzymatic stability. J. Med. Chem. 50, 6201-6211 (2007).
52. Cai M, Kulkarni VV, Hruby VJ. Peptides and peptidomimetics. In: Textbook of Drug Design and Discovery (4th Edition). Larsen-Krogsgaard P, Stromgaard K, Madsen U (Eds). CRC Press, Taylor & Francis, Boca Raton, FL, 123-134 (2010).
53. Kritzer JA. Magic bullets in natures arsenal. Nat. Chem. Biol. 6(8), 566-567 (2010).
54. Stewart ML, Fire E, Keating AE, Walensky LD. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol. 6(8), 595-601 (2010).
55. Sun H, Nikolovska-Coleska Z, Lu J et al. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J. Am. Chem. Soc. 129(49), 15279-15294 (2007). (Pubitemid 350247811)
56. Yin H, Frederick KK, Liu D, Wand AJ, Degrado WF. Arylamide derivatives as peptidomimetic inhibitors of calmodulin. Org. Lett. 8(2), 223-225 (2006). (Pubitemid 43163968)
57. Yin H, Lee G, Sedey KA et al. Terphenyl-based Bak BH3 a-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL. J. Am. Chem. Soc. 127(29), 10191-10196 (2005). (Pubitemid 41045484)
58. Lee JH, Zhang Q, Jo S et al. Novel pyrrolopyrimidine-based a-helix mimetics: cell-permeable inhibitors of protein-protein interactions. J. Am. Chem. Soc. 133(4), 676-679 (2011).
59. Komolov KE, Koch KW. Application of surface plasmon resonance spectroscopy to study G-protein coupled receptor signaling in surface plasmon resonance. In: Methods in Molecular Biology (Vol. 627). De Moi NJ, Fischer MJE (Eds). (Chapter 17), Springer Science, N.Y. (2010).
60. Maurer T. Advancing fragment binders to lead-like compounds using ligand and protein-based NMR spectroscopy. Methods Enzymol. 493, 469-485 (2011).
61. Zhou X, Kini RM. Sivaraman J. Application of isothermal titration calorimetry and column chromatography for identification of biomolecular targets. Nat. Protoc. 6(2), 158-165 (2011).
62. Touchette JC, Williams LL, Ajit D, Gallazzi F, Nichols MR. Probing the amyloid- b(1- 40) fibril environment with substituted tryptophan residues. Arch. Biochem. Biophys. 494(2), 192-197 (2010).
63. Navratilova I, Hopkins AL. Fragment screening by surface plasmon resonance. ACS Med. Chem. Lett. 1(1), 44-48 (2010).
64. Comley J. Progress in the implementation of label-free detection. Drug Discov. World 28-49 (2008).
65. Dahlin AB, Chen S, Jonsson MP, Gunnarsson L, Kall M, Hook F. High-resolution microspectroscopy of plasmonic nanostructures for miniaturizing biosensing. Anal. Chem. 81(16), 6572-6580 (2009).
66. Kirkpatrick P, Ellis C. Chemical Space. Nature 432(7019), 823 (2004).
67. Manly CJ, Chandrasekhar J, Ochterski JW, Hammer JD, Warfield BB. Strategies and tactics for optimizing the hit-to-lead process and beyond - a computational chemistry perspective. Drug Discov. Today 13(3-4), 99-109 (2008).
68. Reynès C, Host H, Camproux AC et al. Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods. PLoS Comput. Biol. 6(3), e1000695 (2010).
69. Venhorst J, Nunez, Kruse GC. Design of a high fragment efficiency library by molecular graph theory. ACS Med. Chem. Lett. 1(9), 499-503 (2010).
70. Schnur DM. Recent trends in library design: rational design revisited. Curr. Opin. Drug Discov. Devel. 11(3), 375-380 (2008). (Pubitemid 351572447)
71. Nielsen TE, Schreiber SL. Towards the optimal screening collection: a synthesis strategy. Angew. Chem. Int. Ed. Engl. 47(1), 48-56 (2008).
72. Schreiber SL. Organic chemistry: molecular diversity by design. Nature 457(7226), 153-154 (2009).
73. Morton D, Leach S, Cordier C, Warriner S, Nelson A. Synthesis of natural-product-like molecules with over eighty distinct scaffolds. Angew. Chem. Int. Ed. Engl. 48(1), 104-109 (2009).
74. Yu N, Bakken GA. Efficient exploration of large combinatorial chemistry spaces by monomer-based similarity searching. J. Chem. Inf. Model. 49(4), 745-755 (2009).
75. Gardiner EJ, Holliday JD, ODowd C, Willett P. Effectiveness of 2D fingerprints for scaffold hopping. Future Med. Chem. 3(4), 405-414 (2011).
76. Geppert H, Bajorath J. Advances in 2D fingerprint similarity searching. Exp. Opin. Drug Discov. 5(6), 529-542 (2010).
77. Zhao H, Akritopoulou-Zanze I. When analoging is not enough: scaffold discovery in medicinal chemistry. Exp. Opin. Drug Discov. 5(2), 123-134 (2010).
78. Clardy J, Walsh C. Lessons from natural molecules. Nature 432(7019), 829-837 (2004). (Pubitemid 40037138)
79. Koneni VS, White KN, Crews P. A selective account of effective paradigms and significant outcomes in the discovery of inspirational marine natural products. J. Nat. Prod. 72(3), 588-603 (2009).
80. Li JW, Vederas JC. Drug discovery and natural products: end of an era or an endless frontier? Science 325(5937), 161-165 (2009).
81. Dancík V, Seiler KP, Young DW, Schreiber SL, Clemons PA. Distinct biological network properties between the targets of natural products and disease genes. J. Am. Chem. Soc. 132(27), 9259-9261.
82. Leach AR, Hann MM, Burrows JN, Griffen EJ. Fragment screening: an introduction. In: Structure-Based Drug Discovery. Hubbard RE (Ed.). RSC Publications, 142-172 (2010).
83. Farmer BT, Reitz AB. Fragment-based drug discovery. In: The Practice of Medicinal Chemistry (4th Edition). Academic Press, London, 228-243 (2008).
84. Hung AW, Ramek A, Wang Y et al. Route to three-dimensional fragments using diversity-oriented synthesis. Proc. Natl Acad. Sci. USA 108(17), 6799-6804 (2011).
85. Whittaker M, Law RJ, Ichihara O, Hesterkamp T, Hallett D. Fragments: past, present and future. Drug Discov. Today 7(3), E163-E171 (2010).
86. Rabal O, Urbano-Cuadrado M, Oyarzabal J. Computational medicinal chemistry in fragment-based drug discovery: what, how and when. Future Med. Chem. 3(1), 95-134 (2011).
87. Whitty A, Kumaravel G. Between a rock and a hard place? Nat. Chem. Biol. 2(3), 112-118 (2006). (Pubitemid 44323856)
88. Tummino PJ, Copeland RA. Residence time of receptor-ligand complexes and its effect on biological function. Biochemistry 47(20), 5481-5492 (2008). (Pubitemid 351711169)
89. Dyhring T, Nielsen E, Sonesson C et al. The dopaminergic stabilizers pridopidine (ACR16) and (-)-OSU6162 display dopamine D(2) receptor antagonism and fast receptor dissociation properties. Eur. J. Pharmacol. 628(1-3), 19-26 (2010).
90. Macarron R, Banks MN, Bojanic D et al. Impact of high-throughput screening in biomedical research. Nat. Rev. Drug Discov. 10(3), 188-195 (2011).
91. Rydzewski M. Turning hits into drugs. In: Real World Drug Discovery. A Chemists Guide to Biotech and Pharmaceutical Research. Elsevier Press, Oxford, UK (2008).
92. Evaluation of enzyme inhibitors in drug discovery: a guide to medicinal chemists and pharmacologists. Copeland RA (Ed.). Wiley-Interscience (2005).
93. Coe JW, Brooks PR, Vetelino MG et al. An a4b2 nicotinic receptor partial agonist for smoking cessation. J. Med. Chem. 48(10), 3474-3477(2005). (Pubitemid 40664098)
94. Galandrin S, Oligny-Longpré G, Bouvier M. The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol. Sci. 28(8), 423-430 (2007). (Pubitemid 47087968)
95. Kenakin T. Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol. Sci. 28(8), 407-415 (2007). (Pubitemid 47087972)
96. Anastassios VT, Zastrow MV, Yudowski GA. b-Blocker drugs mediate calcium signaling in native central nervous system neurons by b-arrestin-biased agonism. Proc. Natl Acad. Sci. USA 107 (49) 21028-21033 (2010).
97. Smith NJ, Bennett KA, Milligan G. When simple agonism is not enough: emerging modalities of GPCR ligands. Mol. Cell Endocrinol. 331(2), 241-247 (2011).
98. Swinney DC, Anthony J. How were new medicines discovered? Nat. Rev. Drug Discov. 10(7), 507-519 (2011).
99. Gleeson MP, Hersey A, Montanari D, Overington J. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat. Rev. Drug Discov. 10(3), 197-208 (2011).
100. Imming P, Sinning C, Meyer A. Drugs, their targets and the nature and number of drug targets. Nat. Rev. Drug Discov. 5(10), 821-834 (2006). (Pubitemid 44480536)
101. Edelstein SJ, Changeux SJJP. Relationships between structural dynamics and functional kinetics in oligomeric membrane receptors. Biophys. J. 98(10), 2045-2052 (2010).
102. Hummer G. Catching a protein in the act. Proc. Natl Acad. Sci. USA 107(6), 2381-2382 (2010).
103. Tadori Y, Forbes RA, McQuade RD, Kikuchi T. Functional potencies of dopamine agonists and antagonists at human dopamine D2 and D3 receptors. Eur. J. Pharmacol. 666(1-3), 43-52 (2011).
104. Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P. The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc. Natl Acad. Sci. USA 105 (36), 13339-13344 (2008).
105. Davidovich C, Bashan A, Auerbach-Nevo T, Yaggie RD, Gontarek RR, Yonath A. Induced-fit tightens pleuromutilins binding to ribosomes and remote interactions enable their selectivity. Proc. Natl Acad. Sci. USA 104(11), 4291-4296 (2007). (Pubitemid 47186219)
106. Freire E. Do enthalpy and entropy distinguish first in class from best in class? Drug Discov. Today 13(19-20), 869-874 (2008).
107. Cohen AF. Developing drug prototypes: pharmacology replaces safety and tolerability? Nat. Rev. Drug Discov. 9(11), 856-865 (2010).
108. Kitano H. A robustness-based approach to systems-oriented drug design. Nat. Rev. Drug Discov. 6(3), 202-210 (2007). (Pubitemid 46344624)
109. Kalgutkar AS, Didiuk MT. Structural alerts, reactive metabolites, and protein covalent binding: how reliable are these attributes as predictors of drug toxicity? Chem. Biodivers. 6(11), 2115-2137 (2009).
110. Kramer JA, Sagartz JE, Morris DL. The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates. Nat. Rev. Drug Discov. 6(8), 636-649 (2007). (Pubitemid 47207750)
111. Gombar VK, Mattioni BE, Zwickl C, Deahl JT. Computational approaches for assessment of toxicity: a historical perspective and current status. In: Computational Toxicology: Risk Assessment for Pharmaceutical and Environmental Chemicals. Ekins S (Ed). Wiley Online Library, 183-215 (2007).
112. Zhu H, Martin TM, Ye L et al. Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure. Chem. Res. Toxicol. 22(12), 1913-1921 (2009).
113. Sedykh A, Zhu H, Tang H et al. Use of in vitro HTS-derived concentration-response data as biological descriptors improves the accuracy of QSAR models of in vivo toxicity. Environ. Health Perspect. 119(3), 364-370 (2011).
114. Kortagere S, Krasowski MD, Ekins S. The importance of discerning shape in molecular pharmacology. Trends Pharmacol. Sci. 30(3), 138-147 (2009).
115. Tanrikulu Y, Schneider G. Pseudoreceptor models in drug design: bridging ligand- and receptor-based virtual screening. Nat. Rev. Drug Discov. 7(8), 667-677 (2008).
116. Hajduk PJ. A question of library design. News and views. Nature 470(7332), 42 (2011).
117. Wolber G, Seidel T, Bendix F, Langer T. Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discov. Today 13(1-2), 23-29 (2008).
118. Mackey MD, Melville JL. Better than random? The chemotype enrichment problem. J. Chem. Inf. Model 49(5), 1154-1162 (2009).
119. Clinciu DL, Chen YF, Ko CN, Lo CC, Yang SM. TSSC: two-stage combinatorial clustering for virtual screening using protein-ligand interactions and physicochemical features. BMC Genom. 11(Suppl. 4), S26 (2010).
120. Coyne AG, Scott DE, Abell C. Drugging challenging targets using fragment-based approaches. Curr. Opin. Chem. Biol. 14(3), 299-307 (2010).
121. Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat. Rev. Drug Discov. 5(12), 993-996 (2006). (Pubitemid 44835126)
122. Borshell N, Papp T, Congreve M. Valuation benefits of structure- Nat. Rev. Drug Discov. 10(3), 166 (2011).
123. DiMasi JA, Faden LB. Competitiveness in follow-on drug R & D: a race or limitation? perspectives. Nat. Rev. Drug Discov. 10(1), 23 (2011).
124. Cressey D. Traditional drug-discovery model ripe for reform. Nature 471(7336), 17-18 (2011).
125. Learning lessons from Pfizers $800 million failure. News feature. Nat. Rev. Drug Discov. 10(3), 163-164 (2011).
126. Douglas FL, Narayanam VK, Mitchell L, Litan RE. The case for entrepreneurship in R&D in the pharmaceutical industry. Nat. Rev. Drug Discov. 9(9), 683-689 (2010).
127. A stronger role for science. Editorial. Nat. Rev. Drug. Discov. 10(3), 159 (2011).
128. A wellcome experiment in seeding drug discovery. News feature. Nat. Rev. Drug Discov. 9(3), 178-180 (2010).
129. Ledford H. Drug buddies. In focus news. Nature 474 (7352), 433-434 (2011).
130. Public sector drug discovery. News in brief. Nat. Rev. Drug Discov. 10(3), 165 (2011).
131. Ashley J. Stevens AJ, Jensen JJ et al. The role of public-sector research in the discovery of drugs and vaccines. N. Engl. J. Med. 364(6), 535-541 (2011).
132. Frye S, Crosby M, Edwards T, Juliano R. US academic drug discovery. News & analysis. Nature 10, 409-410 (2011).
133. Wadman M. NIH encourages translational collaboration with industry. News and analysis. Nat. Rev. Drug Discov. 9(4), 255-256 (2010).
134. An audience with Francis Collins. Nat. Rev. Drug Discov. 10(1), 14 (2011).
135. Wellcome boost for open-access chemistry. News and analysis. Nat. Rev. Drug Discov. 7(10), 789-790 (2008).
136. An audience with Susan Desmond-and analysis. Nat. Rev. Drug Discov. 10(3), 170 (2011).
137. Translational medicine. Career snapshots. Nat. Rev. Drug Discov. 8(7), 593 (2009).
138. Ratner M. Pfizer reaches out to academia- again. Nat. Biotechnol. 29(1), 3-4 (2011).
139. Tralau-Stewart CJ, Wyatt CA, Kleyn DE, Ayad A. Drug discovery: new models for industry-academic partnerships. Drug Discov. Today 14(1/2), 95-101 (2009).
140. Ganellin CR, Mitscher LA, Clement B et al. University education of medicinal chemists: comparison of eight countries. Eur. J. Med. Chem. 35, 163-174 (2000). (Pubitemid 30136698)
141. Krogsgaard-Larsen P, Pelliciari R, De Souza N et al. Medicinal chemistry education: What is needed and where is it going? Drug Dev. Res. 66(1), 1-8 (2006).
142. Hoffmann T, Bishop C. The future of discovery chemistry: quovadis? Academic to industrial - the maturation of medicinal chemistry to chemical biology. Drug Discov. Today 15(7/8) 260-264 (2010).
143. Doyle MP. The evolving nature of chemical education: challenges and opportunities. Future Med. Chem. 2(2), 247-249 (2010).
144. Henry CM. Medicinal chemistry in the classroom. Chem. Eng. News. 81(16), 56 (2003).
145. Giddu S, Subramanian V, Yoon HS, Satyanarayanajois SD. Design of b-hairpin peptides for modulation of cell adhesion by b-turn constraint. J. Med. Chem. 52(3), 726-736 (2009).
146. Gokhale A, Weldeghiorghis TK, Taneja V, Satyanarayanajois SD. Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58. J. Med. Chem. 54(15), 5307-5319 (2011).
147. Hobson K. Former Merck head Vagelos says NIH should stick to basic research. The Wall Street Journal April 15th 2011. ~ http://blogs.wsj.com/ health/2011/04/15/ former-merck-head-vagelos-says-nih-should-stick-to-basic- research/ (Accessed 4 August 2011).