Fragment-based drug discovery

Journal of Medicinal Chemistry

Volumn 47, Issue 14, 2004, Pages 3463-3482

  Erlanson, Daniel A ^a   McDowell, Robert S ^a   O'Brien, Tom ^a  

^a Sunesis Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETOHYDROXAMIC ACID; ADENOSINE KINASE INHIBITOR; ADENYLOSUCCINATE SYNTHASE INHIBITOR; AMINOMETHYLBENZIMIDAZOLE; CASPASE 3 INHIBITOR; COLLAGENASE INHIBITOR; CP 91149; CYCLIN DEPENDENT KINASE INHIBITOR; CYSTEINE PROTEINASE INHIBITOR; ENZYME INHIBITOR; FK 506 BINDING PROTEIN; FK 506 BINDING PROTEIN INHIBITOR; GELATINASE B INHIBITOR; GYRASE INHIBITOR; HYDANTOCIDIN 5' PHOSPHATE; INTERCELLULAR ADHESION MOLECULE 1 INHIBITOR; MATRIX METALLOPROTEINASE INHIBITOR; NAPHTHAMIDINE INHIBITOR; PIPECOLINIC ACID DERIVATIVE; PLASMINOGEN ACTIVATOR INHIBITOR; PROTEIN INHIBITOR; PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR; STROMELYSIN INHIBITOR; THIOSTREPTON; THYMIDYLATE SYNTHASE INHIBITOR; TRIAZINE DERIVATIVE; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; WAY 152177; WAY 170523;

BINDING SITE; COMBINATORIAL CHEMISTRY; DRUG BINDING; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; REVIEW; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE; X RAY CRYSTALLOGRAPHY;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MOLECULAR WEIGHT; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP; TECHNOLOGY, PHARMACEUTICAL;

EID: 3042689621     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040031v     Document Type: Review

References (106)

1. Bohacek, R. S.; McMartin, C.; Guida, W. C. The art and practice of structure-based drug design: A molecular modeling perspective. Med. Res. Rev. 1996, 16, 3-50.
2. Jencks, W. P. On the attribution and additivity of binding energies. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 4046-4050.
3. Nakamura, C. E.; Abeles, R. H. Mode of interaction of β-hydroxy-β-methylglutaryl coenzyme A reductase with strong binding inhibitors: Compactin and related compounds. Biochemistry 1985, 24, 1364-1376.
4. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 1996, 274, 1531-1534.
5. Hann, M. M.; Leach, A. R.; Harper, G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856-864.
6. Murray, C. W.; Verdonk, M. L. The consequences of translational and rotational entropy lost by small molecules on binding to proteins. J. Comput.-Aided Mol. Des. 2002, 16, 741-753.
7. Teague, S. J.; Davis, A. M.; Leeson, P. D.; Oprea, T. The design of leadlike combinatorial libraries. Angew. Chem., Int. Ed. 1999, 38, 3743-3748.
8. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 1997, 23, 3-25.
9. Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. A "rule of three" for fragment-based lead discovery? Drug Discovery Today 2003, 8, 876-877.
10. Bemis, G. W.; Murcko, M. A. The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 1996, 39, 2887-2893.
11. Bemis, G. W.; Murcko, M. A. Properties of known drugs. 2. Side chains. J. Med. Chem. 1999, 42, 5095-5099.
12. Fejzo, J.; Lepre, C. A.; Peng, J. W.; Bemis, G. W.; Ajay; Murcko, M. A.; Moore, J. M. The SHAPES strategy: An NMR-based approach for lead generation in drug discovery. Chem. Biol. 1999, 6, 755-769.
13. Lewell, X. Q.; Judd, D. B.; Watson, S. P.; Hann, M. M. RECAP - retrosynthetic combinatorial analysis procedure: A powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry. J. Chem. Inf. Comput. Sci. 1998, 38, 511-522.
14. Hajduk, P. J.; Bures, M.; Praestgaard, J.; Fesik, S. W. Privileged molecules for protein binding identified from NMR-based screening. J. Med. Chem. 2000, 43, 3443-3447.
15. Jacoby, E.; Davies, J.; Blommers, M. J. Design of small molecule libraries for NMR screening and other applications in drug discovery. Curr. Top. Med. Chem. 2003, 3, 11-23.
16. Vieth, M.; Siegel, M. G.; Higgs, R. E.; Watson, I. A.; Robertson, D. H.; Savin, K. A.; Durst, G. L.; Hipskind, P. A. Characteristic physical properties and structural fragments of marketed oral drugs. J. Med. Chem. 2004, 47, 224-232.
17. Shoichet, B. K.; Stroud, R. M.; Santi, D. V.; Kuntz, I. D.; Perry, K. M. Structure-based discovery of inhibitors of thymidylate synthase. Science 1993, 259, 1445-1450.
18. Erickson, J. A.; Jalaie, M.; Robertson, D. H.; Lewis, R. A.; Vieth, M. Lessons in molecular recognition: The effects of ligand and protein flexibility on docking accuracy. J. Med. Chem. 2004, 47, 45-55.
19. Bohm, H. J. A novel computational tool for automated structure-based drug design. J. Mol. Recognit. 1993, 6, 131-137.
20. Verlinde, C. L.; Rudenko, G.; Hol, W. G. In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach. J. Comput.-Aided Mol. Des. 1992, 6, 131-147.
21. Chau, P. L.; Dean, P. M. Automated site-directed drug design: The generation of a basic set of fragments to be used for automated structure assembly. J. Comput.-Aided Mol. Des. 1992, 6, 385-396.
22. Stultz, C. M.; Karplus, M. Dynamic ligand design and combinatorial optimization: Designing inhibitors to endothiapepsin. Proteins 2000, 40, 258-289.
23. Majeux, N.; Scarsi, M.; Tenette-Souaille, C.; Caflisch, A. Hydrophobicity maps and docking of molecular fragments with solvation. Perspect. Drug Discovery Des. 2000, 20, 145-169.
24. Leach, A. R.; Bryce, R. A.; Robinson, A. J. Synergy between combinatorial chemistry and de novo design. J. Mol. Graphics Modell. 2000, 18, 358-367, 526.
25. Maly, D. J.; Choong, I. C.; Ellman, J. A. Combinatorial target-guided ligand assembly: Identification of potent subtype-selective c-Src inhibitors. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2419-2424.
26. Wang, X.; Choe, Y.; Craik, C. S.; Ellman, J. A. Design and synthesis of novel inhibitors of gelatinase B. Bioorg. Med. Chem. Lett. 2002, 12, 2201-2204.
27. Kehoe, J. W.; Maly, D. J.; Verdugo, D. E.; Armstrong, J. I.; Cook, B. N.; Ouyang, Y. B.; Moore, K. L.; Ellman, J. A.; Bertozzi, C. R. Tyrosylprotein sulfotransferase inhibitors generated by combinatorial target-guided ligand assembly. Bioorg. Med. Chem. Lett. 2002, 12, 329-332.
28. Metz, G.; Ottleben, H.; Vetter, D. Small molecule screening on chemical microarrays. In Protein-Ligand Interactions from Molecular Recognition to Drug Design; Böhm, H.-J., Schneider, G., Eds.; Wiley-VCH: Weinheim, Germany, 2003; pp 213-236.
29. Hajduk, P. J.; Dinges, J.; Schkeryantz, J. M.; Janowick, D.; Kaminski, M.; Tufano, M.; Augeri, D. J.; Petros, A.; Nienaber, V.; Zhong, P.; Hammond, R.; Coen, M.; Beutel, B.; Katz, L.; Fesik, S. W. Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis. J. Med. Chem. 1999, 42, 3852-3859.
30. Huth, J. R.; Sun, C. Utility of NMR in lead optimization: Fragment-based approaches. Comb. Chem. High Throughput Screening 2002, 5, 631-643.
31. Hajduk, P. J.; Sheppard, G.; Nettesheim, D. G.; Olejniczak, E. T.; Shuker, S. B.; Meadows, R. P.; Steinman, D. H.; Carrera, G. M.; Marcotte, P. A.; Severin, J.; Walter, K.; Smith, H.; Gubbins, E.; Simmer, R.; Holzman, T. F.; Morgan, D. W.; Davidsen, S. K.; Summers, J. B.; Fesik, S. W. Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR. J. Am. Chem. Soc. 1997, 119, 5818-5827.
32. Hajduk, P. J.; Dinges, J.; Miknis, G. F.; Merlock, M.; Middleton, T.; Kempf, D. J.; Egan, D. A.; Walter, K. A.; Robins, T. S.; Shuker, S. B.; Holzman, T. F.; Fesik, S. W. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein. J. Med. Chem. 1997, 40, 3144-3150.
33. Hajduk, P. J.; Boyd, S.; Nettesheim, D. G.; Nienaber, V.; Severin, J.; Smith, R.; Davidson, D.; Rockway, T.; Fesik, S. W. Identification of novel inhibitors of urokinase via NMR-based screening. J. Med. Chem. 2000, 43, 3862-3866.
34. Szczepankiewicz, B. G.; Liu, G.; Hajduk, P. J.; Abad-Zapatero, C.; Pei, Z.; Xin, Z.; Lubben, T. H.; Trevillyan, J. M.; Stashko, M. A.; Ballaron, S. J.; Liang, H.; Huang, F.; Hutchins, C. W.; Fesik, S. W.; Jirousek, M. R. Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy. J. Am. Chem. Soc. 2003, 125, 4087-4096.
35. Liu, G.; Xin, Z.; Pei, Z.; Hajduk, P. J.; Abad-Zapatero, C.; Hutchins, C. W.; Zhao, H.; Lubben, T. H.; Ballaron, S. J.; Haasch, D. L.; Kaszubska, W.; Rondinone, C. M.; Trevillyan, J. M.; Jirousek, M. R. Fragment screening and assembly: A highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor. J. Med. Chem. 2003, 46, 4232-4235.
36. Hajduk, P. J.; Gerfin, T.; Boehlen, J. M.; Haberli, M.; Marek, D.; Fesik, S. W. High-throughput nuclear magnetic resonance-based screening. J. Med. Chem. 1999, 42, 2315-2317.
37. 13C- labelled methyl groups. J. Am. Chem. Soc. 2000, 122, 7898-7904.
38. Jahnke, W.; Perez, L. B.; Paris, C. G.; Strauss, A.; Fendrich, G.; Nalin, C. M. Second-site NMR screening with a spin-labeled first ligand. J. Am. Chem. Soc. 2000, 122, 7394-7395.
39. Jahnke, W.; Florsheimer, A.; Blommers, M. J.; Paris, C. G.; Heim, J.; Nalin, C. M.; Perez, L. B. Second-site NMR screening and linker design. Curr. Top. Med. Chem. 2003, 3, 69-80.
40. Sem, D. S.; Pellecchia, M.; Tempczyk-Russel, A. NMR-solve method for rapid identification of bi-ligand drug candidates; Triad Therapeutics, Inc.: San Diego, CA, 2002; U.S. Published Application US20020028468. Unfortunately, Triad Therapeutics is currently in the process of ceasing operations.
41. Hofstadler, S. A.; Griffey, R. H. Analysis of noncovalent complexes of DNA and RNA by mass spectrometry. Chem. Rev. 2001, 101, 377-390.
42. Swayze, E. E.; Jefferson, E. A.; Sannes-Lowery, K. A.; Blyn, L. B.; Risen, L. M.; Arakawa, S.; Osgood, S. A.; Hofstadler, S. A.; Griffey, R. H. SAR by MS: A ligand based technique for drug lead discovery against structured RNA targets. J. Med. Chem. 2002, 45, 3816-3819.
43. He, Y.; Yang, J.; Wu, B.; Robinson, D.; Sprankle, K.; Kung, P.-P.; Lowery, K.; Mohan, V.; Hofstadler, S.; Swayze, E. E.; Griffey, R. Synthesis and evaluation of novel bacterial rRNA-binding benzimidazoles by mass spectrometry. Bioorg. Med. Chem. Lett. 2004, 14, 695-699.
44. Ockey, D. A.; Dotson, J. L.; Struble, M. E.; Stults, J. T.; Bourell, J. H.; Clark, K. R.; Gadek, T. R. Structure-activity relationships by mass spectrometry: Identification of novel MMP-3 inhibitors. Bioorg. Med. Chem. 2004, 12, 37-44.
45. Ockey, D. A.; Gadek, T. R. Discovery of novel PTP1B inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 389-391.
46. Breuker, K. New mass spectrometric methods for the quantification of protein-ligand binding in solution. Angew. Chem., Int. Ed. 2004, 43, 22-25.
47. Tethering is a service mark of Sunesis Pharmaceuticals, Inc. for its fragment-based drug discovery.
48. Erlanson, D. A.; Wells, J. A.; Braisted, A. C. Tethering: Fragment-based drug discovery. Annu. Rev. Biophys. Biomol. Struct. 2004, 33, 199-223.
49. Erlanson, D. A.; Braisted, A. C.; Raphael, D. R.; Randal, M.; Stroud, R. M.; Gordon, E. M.; Wells, J. A. Site-directed ligand discovery. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 9367-9372.
50. Braisted, A. C.; Oslob, J. D.; Delano, W. L.; Hyde, J.; McDowell, R. S.; Waal, N.; Yu, C.; Arkin, M. R.; Raimundo, B. C. Discovery of a potent small molecule IL-2 inhibitor through fragment assembly. J. Am. Chem. Soc. 2003, 125, 3714-3715.
51. Webb, M. E.; Stephens, E.; Smith, A. G.; Abell, C. Rapid screening by MALDI-TOF mass spectrometry to probe binding specificity at enzyme active sites. Chem. Commun. 2003, 2416-2417.
52. Erlanson, D. A.; Lam, J. W.; Wiesmann, C.; Luong, T. N.; Simmons, R. L.; DeLano, W. L.; Choong, I. C.; Burdett, M. T.; Flanagan, W. M.; Lee, D.; Gordon, E. M.; O'Brien, T. In situ assembly of enzyme inhibitors using extended tethering. Nat. Biotechnol. 2003, 21, 308-314.
53. O'Brien, T.; Fahr, B. T.; Sopko, M.; Lam, J. W.; Waal, N. D.; Raimundo, B. C.; Purkey, H.; Pham, P.; Romanowski, M. J. Unpublished results.
54. Mountain, V. Astex, Structural Genomix, and Syrrx. I can see clearly now: Structural biology and drug discovery. Chem. Biol. 2003, 10, 95-98.
55. Sharff, A.; Jhoti, H. High-throughput crystallography to enhance drug discovery. Curr. Opin. Chem. Biol. 2003, 7, 340-345.
56. Mattos, C.; Ringe, D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. 1996, 14, 595-599.
57. Mattos, C.; Ringe, D. Proteins in organic solvents. Curr. Opin. Struct. Biol. 2001, 11, 761-764.
58. Stout, T. J.; Sage, C. R.; Stroud, R. M. The additivity of substrate fragments in enzyme-ligand binding. Structure 1998, 6, 839-848.
59. Nienaber, V. L.; Richardson, P. L.; Klighofer, V.; Bouska, J. J.; Giranda, V. L.; Greer, J. Discovering novel ligands for macromolecules using X-ray crystallographic screening. Nat. Biotechnol. 2000, 18, 1105-1108.
60. Lesuisse, D.; Lange, G.; Deprez, P.; Benard, D.; Schoot, B.; Delettre, G.; Marquette, J. P.; Broto, P.; Jean-Baptiste, V.; Bichet, P.; Sarubbi, E.; Mandine, E. SAR and X-ray. A new approach combining fragment-based screening and rational drug design: Application to the discovery of nanomolar inhibitors of Src SH2. J. Med. Chem. 2002, 45, 2379-2387.
61. Lange, G.; Lesuisse, D.; Deprez, P.; Schoot, B.; Loenze, P.; Benard, D.; Marquette, J. P.; Broto, P.; Sarubbi, E.; Mandine, E. Requirements for specific binding of low affinity inhibitor fragments to the SH2 domain of (pp60)Src are identical to those for high affinity binding of full length inhibitors. J. Med. Chem. 2003, 46, 5184-5195.
62. Congreve, M. S.; Davis, D. J.; Devine, L.; Granata, C.; O'Reilly, M.; Wyatt, P. G.; Jhoti, H. Detection of ligands from a dynamic combinatorial library by X-ray crystallography. Angew. Chem., Int. Ed. 2003, 42, 4479-4482.
63. Ganesan, A. Strategies for the dynamic integration of combinatorial synthesis and screening. Angew. Chem., Int. Ed. 1998, 37, 2828-2831.
64. Ramstrom, O.; Lehn, J. M. Drug discovery by dynamic combinatorial libraries. Nat. Rev. Drug Discovery 2002, 1, 26-32.
65. Skiles, J. W.; Gonnella, N. C.; Jeng, A. Y. The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr. Med. Chem. 2001, 8, 425-474.
66. Skotnicki, J. S.; DiGrandi, M. J.; Levin, J. I. Design strategies for the identification of MMP-13 and TACE inhibitors. Curr. Opin. Drug Discovery Dev. 2003, 6, 742-759.
67. Boehm, H. J.; Boehringer, M.; Bur, D.; Gmuender, H.; Huber, W.; Klaus, W.; Kostrewa, D.; Kuehne, H.; Luebbers, T.; Meunier-Keller, N.; Mueller, F. Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening. J. Med. Chem. 2000, 43, 2664-2674.
68. Fejzo, J.; Lepre, C.; Xie, X. Application of NMR screening in drug discovery. Curr. Top. Med. Chem. 2003, 3, 81-97.
69. Hajduk, P. J.; Gomtsyan, A.; Didomenico, S.; Cowart, M.; Bayburt, E. K.; Solomon, L.; Severin, J.; Smith, R.; Walter, K.; Holzman, T. F.; Stewart, A.; McGaraughty, S.; Jarvis, M. F.; Kowaluk, E. A.; Fesik, S. W. Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J. Med. Chem. 2000, 43, 4781-4786.
70. Liu, G.; Huth, J. R.; Olejniczak, E. T.; Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E. B.; Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. J. Med. Chem. 2001, 44, 1202-1210.
71. Puius, Y. A.; Zhao, Y.; Sullivan, M.; Lawrence, D. S.; Almo, S. C.; Zhang, Z. Y. Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: A paradigm for inhibitor design. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 13420-13425.
72. Salmeen, A.; Andersen, J. N.; Myers, M. P.; Tonks, N. K.; Barford, D. Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol. Cell 2000, 6, 1401-1412.
73. Taylor, S. D.; Kotoris, C. C.; Dinaut, A. N.; Wang, Q.; Ramachandran, C.; Huang, Z. Potent non-peptidyl inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem. 1998, 6, 1457-1468.
74. Jia, Z.; Ye, Q.; Dinaut, A. N.; Wang, Q.; Waddleton, D.; Payette, P.; Ramachandran, C.; Kennedy, B.; Hum, G.; Taylor, S. D. Structure of protein tyrosine phosphatase 1B in complex with inhibitors bearing two phosphotyrosine mimetics. J. Med. Chem. 2001, 44, 4584-4594.
75. Taing, M.; Keng, Y. F.; Shen, K.; Wu, L.; Lawrence, D. S.; Zhang, Z. Y. Potent and highly selective inhibitors of the protein tyrosine phosphatase 1B. Biochemistry 1999, 38, 3793-3803.
76. Guo, X. L.; Shen, K.; Wang, F.; Lawrence, D. S.; Zhang, Z. Y. Probing the molecular basis for potent and selective protein-tyrosine phosphatase 1B inhibition. J. Biol. Chem. 2002, 277, 41014-41022.
77. Asante-Appiah, E.; Patel, S.; Dufresne, C.; Roy, P.; Wang, Q.; Patel, V.; Friesen, R. W.; Ramachandran, C.; Becker, J. W.; Leblanc, Y.; Kennedy, B. P.; Scapin, G. The structure of PTP-1B in complex with a peptide inhibitor reveals an alternative binding mode for bisphosphonates. Biochemistry 2002, 41, 9043-9051.
78. Liu, G.; Xin, Z.; Liang, H.; Abad-Zapatero, C.; Hajduk, P. J.; Janowick, D. A.; Szczepankiewicz, B. G.; Pei, Z.; Hutchins, C. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T. H.; Berg, C. E.; Rondinone, C. M.; Trevillyan, J. M.; Jirousek, M. R. Selective protein tyrosine phosphatase 1B inhibitors: Targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands. J. Med. Chem. 2003, 46, 3437-3440.
79. Tilley, J. W.; Chen, L.; Fry, D. C.; Emerson, S. D.; Powers, G. D.; Biondi, D.; Varnell, T.; Trilles, R.; Guthrie, R.; Mennona, F.; Kaplan, G.; LeMahieu, R. A.; Carson, M.; Han, R.-J.; Liu, C.-M.; Palermo, R.; Ju, G. Identification of a small molecule inhibitor of the IL-2/IL-2Rα receptor interaction which binds to IL-2. J. Am. Chem. Soc. 1997, 119, 7589-7590.
80. Hajduk, P. J.; Shuker, S. B.; Nettesheim, D. G.; Craig, R.; Augeri, D. J.; Betebenner, D.; Albert, D. H.; Guo, Y.; Meadows, R. P.; Xu, L.; Michaelides, M.; Davidsen, S. K.; Fesik, S. W. NMR-based modification of matrix metalloproteinase inhibitors with improved bioavailability. J. Med. Chem. 2002, 45, 5628-5639.
81. Chen, J. M.; Nelson, F. C.; Levin, J. I.; Mobilio, D.; Moy, F. J.; Nilakantan, R.; Zask, A.; Powers, R. Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design. J. Am. Chem. Soc. 2000, 122, 9648-9654.
82. Hanessian, S.; Lu, P. P.; Sanceau, J. Y.; Chemla, P.; Gohda, K.; Fonne-Pfister, R.; Prade, L.; Cowan-Jacob, S. W. An enzyme-bound bisubstrate hybrid inhibitor of adenylosuccinate synthetase. Angew. Chem., Int. Ed. 1999, 38, 3159-3162.
83. 2+, and hadacidin. Biochemistry 1996, 35, 15753-15759.
84. Teresaka, T.; Kinoshita, T.; Kuno, M.; Nakanishi, I. A highly potent non-nucleoside adenosine deaminase inhibitor: Efficient drug discovery by intentional lead hybridization. J. Am. Chem. Soc. 2004, 126, 34-35.
85. Martin, W. H.; Hoover, D. J.; Armento, S. J.; Stock, I. A.; McPherson, R. K.; Danley, D. E.; Stevenson, R. W.; Barrett, E. J.; Treadway, J. L. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1776-1781.
86. Rath, V. L.; Ammirati, M.; Danley, D. E.; Ekstrom, J. L.; Gibbs, E. M.; Hynes, T. R.; Mathiowetz, A. M.; McPherson, R. K.; Olson, T. V.; Treadway, J. L.; Hoover, D. J. Human liver glycogen phosphorylase inhibitors bind at a new allosteric site. Chem. Biol. 2000, 7, 677-682.
87. Oikonomakos, N. G.; Skamnaki, V. T.; Tsitsanou, K. E.; Gavalas, N. G.; Johnson, L. N. A new allosteric site in glycogen phosphorylase B as a target for drug interactions. Struct. Folding Des. 2000, 8, 575-584.
88. Huc, I.; Lehn, J.-M. Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 2106-2110.
89. Nguyen, R.; Huc, I. Using an enzyme's active site to template inhibitors. Angew. Chem., Int. Ed. 2001, 40, 1774-1776.
90. Hochgurtel, M.; Kroth, H.; Piecha, D.; Hofmann, M. W.; Nicolau, C.; Krause, S.; Schaaf, O.; Sonnenmoser, G.; Eliseev, A. V. Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 3382-3387.
91. Hochgurtel, M.; Biesinger, R.; Kroth, H.; Piecha, D.; Hofmann, M. W.; Krause, S.; Schaaf, O.; Nicolau, C.; Eliseev, A. V. Ketones as building blocks for dynamic combinatorial libraries: Highly active neuraminidase inhibitors generated via selection pressure of the biological target. J. Med. Chem. 2003, 46, 356-358.
92. Bramson, H. N.; Corona, J.; Davis, S. T.; Dickerson, S. H.; Edelstein, M.; Frye, S. V.; Gampe, R. T., Jr.; Harris, P. A.; Hassell, A.; Holmes, W. D.; Hunter, R. N.; Lackey, K. E.; Lovejoy, B.; Luzzio, M. J.; Montana, V.; Rocque, W. J.; Rusnak, D.; Shewchuk, L.; Veal, J. M.; Walker, D. H.; Kuyper, L. F. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): Design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J. Med. Chem. 2001, 44, 4339-4358.
93. Nguyen, R.; Huc, I. Optimizing the reversibility of hydrazone formation for dynamic combinatorial chemistry. Chem. Commun. 2003, 942-943.
94. Pang, Y. P.; Quiram, P.; Jelacic, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease. J. Biol. Chem. 1996, 271, 23646-23649.
95. Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.; Williams, I. D.; Pang, Y. P. Dimerization of an inactive fragment of huperzine A produces a drug with twice the potency of the natural product. Angew. Chem., Int. Ed. 2000, 39, 1775-1777.
96. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem., Int. Ed. 2001, 40, 2004-2021.
97. Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radic, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew. Chem., Int. Ed. 2002, 41, 1053-1057.
98. Choong, I. C.; Lew, W.; Lee, D.; Pham, P.; Burdett, M. T.; Lam, J. W.; Wiesmann, C.; Luong, T. N.; Fahr, B.; DeLano, W. L.; McDowell, R. S.; Allen, D. A.; Erlanson, D. A.; Gordon, E. M.; O'Brien, T. Identification of potent and selective small-molecule inhibitors of caspase-3 through the use of extended tethering and structure-based drug design. J. Med. Chem. 2002, 45, 5005-5022.
99. Vassilev, L. T.; Vu, B. T.; Graves, B.; Carvajal, D.; Podlaski, F.; Filipovic, Z.; Kong, N.; Kammlott, U.; Lukacs, C.; Klein, C.; Fotouhi, N.; Liu, E. A. In vivo activation of the p53 pathway by small-molecule antagonists of mdm2. Science 2004, 303, 844-848.
100. Rishton, G. M. Nonleadlikeness and leadlikeness in biochemical screening. Drug Discovery Today 2003, 8, 86-96.
101. 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.
102. McGovern, S. L.; Shoichet, B. K. Kinase inhibitors: Not just for kinases anymore. J. Med. Chem. 2003, 46, 1478-1483.
103. McGovern, S. L.; Helfand, B. T.; Feng, B.; Shoichet, B. K. A specific mechanism of nonspecific inhibition. J. Med. Chem. 2003, 46, 4265-4272.
104. Ryan, A. J.; Gray, N. M.; Lowe, P. N.; Chung, C. W. Effect of detergent on "promiscuous" inhibitors. J. Med. Chem. 2003, 46, 3448-3451.
105. Gill, A. New lead generation strategies for protein kinase inhibitors-fragment based screening approaches. Mini-Rev. Med. Chem. 2004, 4, 301-311.
106. Fattori, D. Molecular recognition: The fragment approach in lead generation. Drug Discovery Today 2004, 9, 229-238.