Fragment-based drug discovery and molecular docking in drug design

Current Pharmaceutical Biotechnology

Volumn 16, Issue 1, 2015, Pages 11-25

  Wang, Tao ^a   Wu, Mian Bin ^a,b   Chen, Zheng Jie ^b   Chen, Hua ^b   Lin, Jian Ping ^a   Yang, Li Rong ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b Zhejiang Key Laboratory of Antifungal Drugs   (China)

Author keywords

Drug candidate; Drug design; Drug discovery; FBDD; Molecular docking; Virtual screening

Indexed keywords

(E) N (4 OXOPENT 2 ENYL) 3 PTOLYLISOXAZOLE 5 CARBOXAMIDE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL) PROPYLAMINO] 3 NITROBENZENESULFONYL] BENZAMIDE; 6 (2 FLUOROPYRIDIN 4 YL)PYRIDO[3 2 D]PYRIMIDIN 4 AMINE; 6 AZAINDAZOLE; ANTINEOPLASTIC AGENT; AT24111; AT7519; B RAF KINASE; GSK2696124A; HJC0123; LY5; MELK T1; MISCELLANEOUS DRUGS AND AGENTS; N (3 5 DIMETHYLPHENYL) 4 ((2 ETHYL 3 4 DIHYDROQUINAZOLIN 6 YL) METHYLAMINO)BENZENESULFONAMIDE; N (5 (TERT BUTYL)ISOXAZOL 3 YL) 2 (4 (IMIDAZO[1 2 A]PYRIDIN 6 YL)PHENYL)ACETAMIDE; NAVITOCLAX; PROTEIN BCL XL; UNCLASSIFIED DRUG; VEMURAFENIB;

ALGORITHM; ARTICLE; BINDING AFFINITY; BINDING AND RELATED PHENOMENA; BIO LAYER INTERFEROMETRY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG SCREENING; FRAGMENT BASED DRUG DISCOVERY; HUMAN; INTERFEROMETRY; ISOTHERMAL TITRATION CALORIMETRY; LIGAND RECEPTOR INTERACTION; MASS SPECTROMETRY; MOLECULAR DOCKING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHASE 2 CLINICAL TRIAL (TOPIC); SCORING SYSTEM; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE; X RAY CRYSTALLOGRAPHY; DRUG DEVELOPMENT; PROCEDURES;

DRUG DISCOVERY; HUMANS; MOLECULAR DOCKING SIMULATION;

EID: 84921838527     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/1389201015666141122204532     Document Type: Article

References (117)

1. Shekhar, M.P. Drug resistance: challenges to effective therapy. Curr. Cancer Drug Targets, 2011, 11(5), 613-623.
2. Murray, C.W.; Rees, D.C. The rise of fragment-based drug discovery. Nat. Chem., 2009, 1(3), 187-192.
3. Xiang, M.; Cao, Y.; Fan, W.; Chen, L.; Mo, Y. Computer-aided drug design: Lead discovery and optimization. Combinat. Chem. High Throughput Screen., 2012, 15(4), 328-337.
4. Sliwoski, G.; Kothiwale, S.; Meiler, J.; Lowe, E.W.; Jr. Computational methods in drug discovery. Pharmacol. Rev., 2014, 66(1), 334-395.
5. Michel, J. Current and emerging opportunities for molecular simulations in structure-based drug design. Phys. Chem. Chem. Phys., 2014, 16(10), 4465-4477.
6. Juillerat-Jeanneret, L.; Schmitt, F. Chemical modification of therapeutic drugs or drug vector systems to achieve targeted therapy: Looking for the grail. Med. Res. Rev., 2007, 27(4), 574-590.
7. Newman, D.J. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J. Med. Chem., 2008, 51(9), 2589-2599.
8. Harvey, A.L. Natural products as a screening resource. Curr. Opin. Chem. Biol., 2007, 11, 480-484.
9. Galm, U.; Shen, B. Natural product drug discovery: the times have never been better. Chem. Biol., 2007, 14(10), 1098-1104.
10. Nikapitiya, C. Bioactive secondary metabolites from marine microbes for drug discovery. Adv. Food Nutr. Res., 2012, 65, 363-87.
11. Gribbon, P.; Andreas, S. High-throughput drug discovery: what can we expect from HTS? Drug Discov. Today, 2005, 10(1), 17-22.
12. Joseph-McCarthy, D.; Campbell, A.J.; Kern, G.; Moustakas, D. Fragment-based lead discovery and design. J. Chem. Inf. Model., 2014, 54(3), 693-704.
13. Edink, E.; Rucktooa, P.; Retra, K.; Akdemir, A.; Nahar, T.; Zuiderveld, O.; Elk, Rev.; Janssen, E.; Nierop, P.; Muijlwijk- Koezen, J.; Smit, A.B.; Sixma, T.K.; Leurs, R.; Esch, I.J. Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis. J. Am. Chem. Soc., 2011, 133(14), 5363-5371.
14. Bollag, G.; Hirth, P.; James, Tsai.; Zhang, J.; Ibrahim, P.; Cho, H.; Spevak, W.; Zhang, C.; Zhang, Y.; Habets, G.; Burton, E.A.; Wong, B.; Tsang, G.; West, B.L.; Powell, B.; Shellooe, R.; Marimuthu, A.; Nguyen, H.; Zhang, K.Y.J.; Artis, D.; Schlessinger, J.; Su, F.; Higgins, B.; Iyer, R.; D'Andrea, K.; Koehler, A.; Stumm, M.; Lin, P.S.; Lee, R.J.; Grippo, J.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.; Chapman, P.B.; Flaherty, K.; Xu, X.; Nathanson, K.L.; Nolop, K. Clinical efficacyof a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
15. Muegge, I.; Oloff, S. Advances in virtual screening. Drug Discov. Today: Technol., 2007, 3, 405-411.
16. Chen, H.; Lyn, P.D.; Giordanetto, F.; Lovell, T.; Li, J. On evaluating molecular-docking methods for pose prediction and enrichment factors. J. Chem. Inf. Model., 2006, 48(1), 401-415.
17. Lang, P.T.; Aynechi, T.; Moustakas, D.; Shoichet, B.; Kuntz, I.D.; Brooijmans, N.; Oshiro, C.M.; Huang, Z. Drug discovery research: new frontiers in the post-genomic era, Wiley & Sons: New York , 2007, 1-23.
18. Chen, Y.; Shoichet, B.K. Molecular docking and ligand specificity in fragment-based inhibitor discovery. Nat. Chem. Biol., 2009, 5(5), 358-364.
19. Lyne, P.D.; Lamb, M.L.; Saeh, J.C. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J. Med. Chem., 2006, 49(16), 4805-4808.
20. Hessler, G.; Baringhaus, K.H. The scaffold hopping potential of pharmacophores. Drug Discov. Today: Technol., 2010, 7(4), 263- 270.
21. Maggiora, G.; Vogt, M.; Stumpfe, D.; Bajorath, J. Molecular similarity in medicinal chemistry. J. Med. Chem., 2014, 57, 3186-3204.
22. De Beer, T.; Wells, G.; Burger, P.; Joubert, F.; Marechal, E.; Birkholtz, L.; Louw, A.; Antimalarial drug discovery: in silico structural biology and rational drug design. Infect. Disord. Drug Targets, 2009, 9(3), 304-318.
23. 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 Deliv. Rev., 2001, 46(1-3), 3-26.
24. Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. A 'rule of three' for fragment-based lead discovery? Drug Discov. Today, 2003, 8(19), 876-877.
25. Leeson, P.D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov., 2007, 6(11), 881-890.
26. Gleeson, M.P. Generation of a set of simple, interpretable ADMET rules of thumb. J. Med. Chem., 2008, 51(4), 817-834.
27. Colclough, N.; Hunter, A.; Kenny, P.W.; Kittlety, R.S.; Lobedan, L.; Tam, K.Y.; Timms, M.A. High throughput solubility determination with application to selection of compounds for fragment screening. Bioorg. Med. Chem., 2008, 16(13), 6611-6616.
28. Price, D.A.; Blagg, J.; Jones, L.; Greene, N.; Wager, T. Physiochemical drug properties associated with in vivo toxicological outcomes. Expert Opin. Drug Metab. Toxicol., 2008, 5(8), 921-931.
29. Erlanson, D.A. Introduction to fragment-based drug discovery. Top. Curr. Chem., 2012, 317, 1-32.
30. Schuffenhauer, A.; Ruedisser, S.; Marzinzik, A.L.; Jahnke, W.; Blommers, M.; Selzer, P.; Jacoby, E. Library design for fragment based screening. Curr. Top. Med. Chem., 2005, 5(8), 751-762.
31. Chung, C.W.; Dean, A.W.; Woolven, J.M.; Bamborough, P. Fragment- based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery. J. Med. Chem., 2012, 55(2), 576-586.
32. Hillisch, A.; Pineda, L.F.; Hilgenfeld, R. Utility of homology models in the drug discovery process. Drug Discov. Today, 2004, 9(15), 659-669.
33. Blundell, T.L.; Jhoti, H.; Abell, C. High-throughput crystallography for lead discovery in drug design. Nat. Rev. Drug Discov., 2002, 1(1), 45-54.
34. Shuker, S.B.; Hajduk, P.J.; Meadows, R.P.; Fesik, S.W. Discovering high-affinity ligands for proteins: SAR by NMR. Science, 1996, 274(5292), 1531-1534.
35. 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(26), 5628-5639.
36. Wada, C.K. The evolution of the matrix metalloproteinase inhibitor drug discovery program at Abbott Laboratories. Curr. Top Med. Chem., 2004, 4(12), 1255-1267.
37. Cala, O.; Guilliere, F.; Krimm, I. NMR-based analysis of proteinligand interactions. Anal. Bioanal. Chem., 2014, 406(4), 943-956.
38. Mayer, M.; Meyer, B. Characterization of ligand binding by caturation transfer difference NMR spectroscopy. Angew. Chem. Int. Ed., 1999, 38, 1784-1788.
39. Becattini, B.; Pellecchia, M. SAR by ILOEs: An NMR-based approach to reverse chemical genetics. Chemistry, 2006, 12(10), 2658-2662.
40. Becattini, B.; Culmsee, C.; Leone, M.; Zhai, D.; Zhang, X.; Crowell, K.J.; Rega, M.F.; Landshamer, S.; Reed, J.C.; Plesnila, N.; Pellecchia, M. Structure-activity relationships by interligand NOEbased design and synthesis of antiapoptotic compounds targeting Bid. Proc. Natl. Acad. Sci. USA, 2006, 103(33), 12602-12606.
41. Eddy, M.T.; Belenky, M.; Sivertsen, A.C.; Griffin, R.G.; Herzfeld, J. Selectively dispersed isotope labeling for protein structure determination by magic angle spinning NMR. J. Biomol. NMR., 2013, 57(2), 129-139.
42. Vanwetswinkel, S.; Heetebrij, R.J.; van Duynhoven, J.; Hollander, J.G.; Filippov, D.V.; Hajduk, P.J.; Siegal, G. TINS, target immobilized NMR screening: An efficient and sensitive method for ligand discovery. Chem. Biol., 2005, 12(2), 207-216.
43. Fruh, V.; Zhou, Y.; Chen, D.; Loch, C.; Ab, E.; Grinkova, Y.N.; Verheij, H.; Sligar, S.G.; Bushweller, J.H.; Siegal, G. Application of fragment-based drug discovery to membrane proteins: identification of ligands of the integral membrane enzyme DsbB. Chem. Biol., 2010, 17(8), 881-891.
44. Hartshorn, M.J.; Murray, C.W.; Cleasby, A.; Frederickson, M.; Tickle, I.J.; Jhoti, H. Fragment-based lead discovery using X-ray crystallography. J. Med. Chem., 2005, 48(2), 403-413.
45. Jhoti, H.; Cleasby, A.; Verdonk, M.; Williams, G. Fragment-based screening using X-ray crystallography and NMR spectroscopy. Curr. Opin. Chem. Biol., 2007, 11(5), 485-493.
46. Wasserman, S.R.; Koss, J.W.; Sojitra, S.T.; Morisco, L.L.; Burley, S.K. Rapid-access, high-throughput synchrotron crystallography for drug discovery. Trends Pharmacol. Sci., 2012, 33(5), 261-267.
47. Davis, A.M.; St-Gallay, S.A.; Kleywegt, G.J. Limitations and lessons in the use of X-ray structural information in drug design. Drug Discov. Today, 2008, 13(19-20), 831-841.
48. Sondergaard, C.R.; Garrett, A.E.; Carstensen, T.; Pollastri, G.; Nielsen, J.E. Structural artifacts in protein-ligand X-ray structures: implications for the development of docking scoring functions. J. Med. Chem., 2009, 52(18), 5673-5684.
49. Hou, W.; Cronin, S.B. A review of surface plasmon resonanceenhanced photocatalysis. Adv. Funct. Mater., 2013, 23, 1612-1619.
50. Retra, K.; Irth, H.; van Muijlwijk-Koezen, J.E. Surface Plasmon Resonance biosensor analysis as a useful tool in FBDD. Drug Discov. Today: Technol., 2010, 7, 181-187.
51. Rich, R.L.; Myszka, D.G. Kinetic analysis and fragment screening with Fujifilm AP-3000. Anal. Biochem., 2010, 402(2), 170-178.
52. Nordstrom, H.; Gossas, T.; Hämäläinen, M.; Källblad, P.; Nyström, S.; Wallber, H.; Danielson, U.H. Identification of MMP-12 inhibitors by using biosensor-based screening of a fragment library. J. Med. Chem., 2008, 51(12), 3449-3459.
53. Rich, R.L.; Myszka, D.G. Grading the commercial optical biosensor literature-class of 2008: the mighty binders. J. Mol. Recognit., 2010, 23(1), 1-64.
54. Wallner, J.; Lhota, G.; Jeschek, D.; Mader, A.; Vorauer-Uhl, K. Application of Bio-Layer Interferometry for the analysis of protein/ liposome interactions. J. Pharm. Biomed. Anal., 2013, 72, 150- 154.
55. Fang, Y. Ligand-receptor interaction platforms and their applications for drug discovery. Expert Opin. Drug Discov., 2012, 7(10), 969-988.
56. Wartchow, C.A.; Podlaski, F.; Li, S.; Rowan, K.; Zhang, X.; Mark, D.; Huang, K.S. Biosensor-based small molecule fragment screening with biolayer interferometry. J. Comput. Aided Mol. Des., 2011, 25(7), 669-676.
57. Torres, F.E.; Recht, M.I.; Coyle, J.E.; Bruce, R.H.; Williams, G. Higher throughput calorimetry: opportunities, approaches and challenges. Curr. Opin. Struct. Biol., 2010, 20(5), 598-605.
58. Garbett, N.C.; Chaires, J.B. Thermodynamic studies for drug design and screening. Expert Opin. Drug Discov., 2012, 7(4), 299- 314.
59. Recht, M.I.; Sridhar, V.; Badger, J.; Bounaud, P.Y.; Logan, C.; Chie-Leon, B.; Nienaber, V.; Torres, F.E. Identification and optimization of PDE10A inhibitors using fragment-based screening by nanocalorimetry and X-ray crystallography. J. Biomol. Screen., 2013, 19(4), 497-507.
60. Casale, E.; Amboldi, N.; Brasca, M.G.; Caronni, D.; Colombo, N.; Dalvit, C.; Felder, E.R.; Fogliatto, G.; Galvani, A.; Isacchi, A.; Polucci, P.; Riceputi, L.; Sola, F.; Visco, C.; Zuccotto, F.; Casuscelli, F. Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors. Bioorg. Med. Chem., 2014, 22(15), 4135-4150.
61. Zhang, Z.; Liu, C.; Li, X.; Song, T.; Wu, Z.; Liang, X.; Zhao, Y.; Shen, X.; Chen, H. Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2- hydroxynicotinamide derivatives as novel Mcl-1 inhibitors. Eur. J. Med. Chem., 2013, 60, 410-420.
62. Banerjee, D.R.; Dutta, D.; Saha, B.; Bhattacharyya, S.; Senapati, K.; Das, A.K.; Basak, A. Design, synthesis and characterization of novel inhibitors against mycobacterial β -ketoacyl CoA reductase FabG4. Org. Biomol. Chem., 2014, 12(1), 73-85.
63. Hofstadler, S.A.; Sannes-Lowery, K.A. Applications of ESI-MS in drug discovery: interrogation of noncovalent complexes. Nat. Rev. Drug. Discov., 2006, 5(7), 585-595.
64. Tjernberg, A.; Carnö, S.; Oliv, F.; Benkestock, K.; Edlund, P.O.; Griffiths, W.J.; Hallén, D. Determination of dissociation constants for protein-ligand complexes by electrospray ionization mass spectrometry. Anal. Chem., 2004, 76(15), 4325-4331.
65. Duffell, K.M; Hudson, S.A.; McLean, K.J.; Munro, A.W.; Abell, C.; Matak-Vinkovic, D. Nanoelectrospray ionization mass spectrometric study of Mycobacterium tuberculosis CYP121-ligand interactions. Anal. Chem., 2013, 85(12), 5707-5714.
66. Mulabagal, V.; Calderon, A.I. Development of an ultrafiltrationliquid chromatography/mass spectrometry (UF-LC/MS) based ligand-binding assay and an LC/MS based functional assay for Mycobacterium tuberculosis shikimate kinase. Anal. Chem., 2010, 82(9), 3616-3621.
67. El-Hawiet, A.; Kitova, E.N.; Klassen, J.S. Quantifying carbohydrate- protein interactions by electrospray ionization mass spectrometry analysis. Biochemistry, 2012, 51(21), 4244-4253.
68. Maple, H.J.; Garlish, R.A.; Rigau-Roca, L.; Porter, J.; Whitcombe, I.; Prosser, C.E.; Kennedy, J.; Henry, A.J.; Taylor, R.J.; Crump, M.P.; Crosby, J. Automated protein-ligand interaction screening by mass spectrometry. J. Med. Chem., 2012, 55(2), 837-851.
69. Cubrilovic, D.; Haap, W.; Barylyuk, K.; Ruf, A.; Badertscher, M.; Gubler, M.; Tetaz, T.; Joseph, C.; Benz, J.; Zenobi, R. Determination of protein-ligand binding constants of a cooperatively regulated tetrameric enzyme using electrospray mass spectrometry. ACS Chem. Biol., 2014, 9(1), 218-226.
70. Chen, X.; Li, L.; Chen, S.; Xu, Y.; Xia, Q.; Guo, Y.; Liu, X.; Tang, Y.; Zhang, T.; Chen, Y. Identification of inhibitors of the antibiotic- resistance target new delhi metallo-β-lactamase 1 by both nanoelectrospray ionization mass spectrometry and ultrafiltration liquid chromatography/mass spectrometry approaches. Anal. Chem., 2013, 85(16), 7957-7965.
71. Silvestre, H.L.; Blundell, T.L.; Abell, C.; Ciulli, A. Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery. Proc. Natl. Acad. Sci. USA, 2013, 110(32), 12984-12989.
72. Siegal, G.; Ab, E.; Schultz, J. Integration of fragment screening and library design. Drug Discov. Today, 2007, 12(23-24), 1032-1039.
73. Jhoti, H.; Williams, G.; Rees, D.C.; Murray, C.W. The 'rule of three' for fragment-based drug discovery: Where are we now? Nat. Rev. Drug Discov., 2013, 12(8), 644-645.
74. Kohlmann, A.; Zech, S.G.; Li, F.; Zhou, T.; Squillace, R.M.; Commodore, L.; Greenfield, M.T.; Lu, X.; Miller, D.P.; Huang, W.S.; Qi, J.; Thomas, R.M.; Wang, Y.; Zhang, S.; Dodd, R.; Liu, S.; Xu, R.; Xu, Y.; Miret, J.J.; Rivera, V.; Clackson, T.; Shakespeare, W.C.; Zhu, X.; Dalgarno, D.C. Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors. J. Med. Chem., 2013, 56(3), 1023-1040.
75. Edink, E.; Rucktooa, P.; Retra, K.; Akdemir, A.; Nahar, T.; Zuiderveld, O.; van Elk, R.; Janssen, E.; van Nierop, P.; van Muijlwijk-Koezen, J.; Smit, A.B.; Sixma, T.K.; Leurs, R.; de Esch, I.J. Fragment growing induces conformational changes in acetylcholine- binding protein: A structural and thermodynamic analysis. J. Am. Chem. Soc., 2011, 133(14), 5363-5371.
76. Schmidt-Kittler, O.; Zhu, J.; Yang, J.; Liu, G.; Hendricks, W.; Lengauer, C.; Gabelli, S.B.; Kinzler, K.W.; Vogelstein, B.; Huso, D.L. PI3Kα inhibitors that inhibit metastasis. Oncotarget, 2010, 1(5), 339-348.
77. Ichihara, O.; Barker, J.; Law, R.J.; Whittaker, M. Compound design by fragment-linking. Mol. Inform., 2011, 30, 298-306.
78. Sledz, P.; Silvestre, H.L.; Hung, A.W.; Ciulli, A.; Blundell, T.L.; Abell, C. Optimization of the interligand overhauser effect for fragment linking: application to inhibitor discovery against mycobacterium tuberculosis pantothenate synthetase. J. Am. Chem. Soc., 2010, 132(13), 4544-4545.
79. Barker, J.J.; Barker, O.; Courtney, S.M.; Gardiner, M.; Hesterkamp, T.; Ichihara, O.; Mather, O.; Montalbetti, C.A.; Muller, A.; Varasi, M.; Whittaker, M.; Yarnold, C.J. Discovery of a novel Hsp90 inhibitor by fragment linking. Chem. Med. Chem., 2010, 5(10), 1697-1700.
80. Taylor, S.J.; Padyana, A.K.; Abeywardane, A.; Liang, S.; Hao, M.H.; De Lombaert, S.; Proudfoot, J.; Farmer, B.S.; Li, X.; Collins, B.; Martin, L.; Albaugh, D.R.; Hill-Drzewi, M.; Pullen, S.S.; Takahashi, H. Discovery of potent, selective chymase inhibitors via fragment linking strategies. J. Med. Chem., 2013, 56(11), 4465- 4481.
81. Talele, T.T.; Khedkar, S.A.; Rigby, A.C. Successful applications of computer aided drug discovery: Moving drugs from concept to the clinic. Curr. Top. Med. Chem., 2010, 10(1), 127-141.
82. Talamas, F.X.; Ao-Ieong, G.; Brameld, K.A.; Chin, E.; de Vicente, J.; Dunn, J.P.; Ghate, M.; Giannetti, A.M.; Harris, S.F.; Labadie, S.S.; Leveque, V.; Li, J.; Lui, A.S.; McCaleb, K.L.; Najera, I.; Schoenfeld, R.C.; Wang, B.; Wong, A. De novo fragment design: a medicinal chemistry approach to fragment-based lead generation. J. Med. Chem., 2013, 56(7), 3115-3119.
83. Loving, K.; Salam, N.K.; Sherman, W. Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation. J. Comput. Aided Mol. Des., 2009, 23(8), 541-554.
84. Thangapandian, S.; John, S.; Sakkiah, S.; Lee, K.W. Ligand and structure based pharmacophore modeling to facilitate novel histone deacetylase 8 inhibitor design. Eur. J. Med. Chem., 2010, 45(10), 4409-4417.
85. Thangapandian, S.; John, S.; Sakkiah, S.; Lee, K.W. Potential virtual lead identification in the discovery of renin inhibitors: Application of ligand and structure-based pharmacophore modeling approaches. Eur. J. Med. Chem., 2011, 46(6), 2469-2476.
86. Chen, C.; Wang, T.; Wu, F.; Huang, W.; He, G.; Ouyang, L.; Xiang, M.; Peng, C.; Jiang, Q. Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity. Drug Des. Devel. Ther., 2014, 8, 1195-1210.
87. Muegge, I.; Oloff, S. Advances in virtual screening. Drug Discov. Today: Techno., 2006, 3, 405-411.
88. Meng, X.Y.; Zhang, H.X.; Mezei, M.; Cui, M. Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput. Aided Drug Des., 2011, 7(2), 146-157.
89. Halperin, I.; Ma, B.; Wolfson, H.; Nussinov, R. Principles of docking: an overview of search algorithms and a guide to scoring functions. Proteins, 2002, 47(4), 409-443.
90. Teague, S.J. Implications of protein flexibility for drug discovery. Nat. Rev. Drug Discov., 2003, 2(7), 527-541.
91. Marcou, G.; Rognan, D. Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. J. Chem. Inf. Model., 2007, 47(1), 195-207.
92. Klebe, G. Virtual ligand screening: Strategies, perspectives and limitations. Drug Discov. Today, 2006, 11(13-14), 580-594.
93. Cross, J.B.; Thompson, D.C.; Rai, B.K.; Baber, J.C.; Fan, K.Y.; Hu, Y.; Humblet, C. Comparison of several molecular docking programs pose prediction and virtual screening accuracy. J. Chem. Inf. Model., 2009, 49(6), 1455-1474.
94. Bollag, G.; Hirth, P.; Tsai, J.; Zhang, J.; Ibrahim, P.N.; Cho, H.; Spevak, W.; Zhang, C.; Zhang, Y.; Habets, G.; Burton, E.A.; Wong, B.; Tsang, G.; West, B.L.; Powell, B.; Shellooe, R.; Marimuthu, A.; Nguyen, H.; Zhang, K.Y.; Artis, D.R.; Schlessinger, J.; Su, F.; Higgins, B.; Iyer, R.; D'Andrea, K.; Koehler, A.; Stumm, M.; Lin, P.S.; Lee, R.J.; Grippo, J.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.A.; Chapman, P.B.; Flaherty, K.T.; Xu, X.; Nathanson, K.L.; Nolop, K. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
95. Tsai, J.; Lee, J.T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N.K.; Sproesser, K.; Li, L.; Smalley, K.S.; Fong, D.; Zhu, Y.L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.; Suzuki, Y.; Luu, C.; Settachatgul, C.; Shellooe, R.; Cantwell, J.; Kim, SH.; Schlessinger, J.; Zhang, K.Y.; West, B.L.; Powell, B.; Habets, G.; Zhang, C.; Ibrahim, P.N.; Hirth, P.; Artis, D.R.; Herlyn, M.; Bollag, G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl. Acad. Sci. U.S.A, 2008, 105(8), 3041-3046.
96. Bollag, G.; Hirth, P.; James, Tsai.; Zhang, J.; Ibrahim, P.; Cho, H.; Spevak, W.; Zhang, C.; Zhang, Y.; Habets, G.; Burton, E.A.; Wong, B.; Tsang, G.; West, B.L.; Powell, B.; Shellooe, R.; Marimuthu, A.; Nguyen, H.; Zhang, K.Y.; Artis, D.R.; Schlessinger, J.; Su, F.; Higgins, B.; Iyer, R.; D'Andrea, K.; Koehler, A.; Stumm, M.; Lin, P.S.; Lee, R.J.; Grippo, J.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.; Chapman, P.B.; Flaherty, K.; Xu, X.; Nathanson, K.L.; Nolop, K. Clinical efficacyof a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
97. Flaherty, K.T.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.A.; O'Dwyer, P.J.; Lee R.J.; Grippo, J.F.; Nolop, K.; Chapman, P.B. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med., 2010, 363(9), 809-819.
98. Yang, H.; Higgins, B.; Kolinsky, K.; Packman, K.; Go, Z.; Iyer, R.; Kolis, S.; Zhao, S.; Lee, R.; Grippo, J.F.; Schostack, K.; Simcox, M.E.; Heimbrook, D.; Bollag, G.; Su, F. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res., 2010, 70(13), 5518- 5527.
99. Wyatt, P.G.; Woodhead, A.J.; Berdini, V.; Boulstridge, J.A.; Carr, M.G.; Cross, D.M.; Davis, D.J.; Devine, L.A.; Early, T.R.; Feltell, R.E. Identification of N-(4-Piperidinyl)-4-(2, 6- dichlorobenzoylamino)-1 H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based Xray crystallography and structure based drug design. J. Med. Chem., 2008, 51(16), 4986-4999.
100. Hartshorn, M.J.; Murray, C.W.; Cleasby, A.; Frederickson, M.; Tickle, I.J.; Jhoti, H. Fragment-based lead discovery using X-ray crystallography. J. Med. Chem., 2005, 48(2), 403-413.
101. Wyatt, P.G.; Woodhead, A.J.; Berdini, V.; Boulstridge, J.A.; Carr, M.G.; Cross, D.M.; Davis, D.J.; Devine, L.A.; Early, T.R.; Feltell, R.E.; Lewis, E.J.; McMenamin, R.L.; Navarro, E.F.; O'Brien, M.A.; O'Reilly, M.; Reule, M.; Saxty, G.; Seavers, L.C.A.; Smith, D.M.; Squires, M.S.; Trewartha, G.; Walker, M.T.; Woolford, A.J.A. Identification of N-(4-Piperidinyl)-4-(2,6- dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based XRay crystallography and structure based drug design. J. Med. Chem., 2008, 51(16), 4986-4999.
102. Arkin, M.R.; Wells, J.A. Small-molecule inhibitors of proteinprotein interactions: progressing towards the dream. Nat. Rev. Drug Discov., 2004, 3(4), 301-317.
103. Oltersdorf, T.; Elmore, S.W.; Shoemaker, A.R.; Armstrong, R.C.; Augeri, D.J.; Belli, B.A.; Bruncko, M.; Deckwerth, T.L.; Dinges, J.; Hajduk, P.J.; Joseph, M.K.; Kitada, S.; Korsmeyer, S.J.; Kunzer, A.R.; Letai, A.; Li, C.; Mitten, M.J.; Nettesheim, D.G.; Ng. S.; Nimmer, PM.; O'Connor, J.M.; Oleksijew, A.; Petros, A.M.; Reed, J.C.; Shen, W.; Tahir, S.K.; Thompson, C.B.; Tomaselli, K.J.; Wang, B.; Wendt, M.D.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 2005, 435(7042), 677-681.
104. Petros, A.M.; Dinges, J.; Augeri, D.J.; Baumeister, S.A.; Betebenner, D.A.; Bures, M.G.; Elmore, S.W.; Hajduk, P.J.; Joseph, M.K.; Landis, S.K.; Nettesheim, D.G.; Rosenberg, S.H.; Shen, W.; Thomas, S.; Wang, X.; Zanze, I.; Zhang, H.; Fesik, S.W. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xLfrom NMR and parallel synthesis. J. Med. Chem., 2006, 49(2), 656-663.
105. Wendt, M.D.; Shen, W.; Kunzer, A.; McClellan, W.J.; Bruncko, M.; Oost, T.K.; Ding, H.; Joseph, M.K.; Zhang, H.; Nimmer, P.M.; Ng S.C.; Shoemaker, A.R.; Petros, A.M.; Oleksijew, A.; Marsh, K.; Bauch, J.; Oltersdorf, T.; Belli, B.A.; Martineau, D.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W. 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., 2006, 49(3), 1165-1181.
106. Bruncko, M.; Oost, T.K.; Belli, B.A.; Ding, H.; Joseph, M.K.; Kunzer, A.; Martineau, D.; McClellan, W.J.; Mitten, M.; Ng S.C; Nimmer, P.M.; Oltersdorf, T.; Park, C.M.; Petros, A.M.; Shoemaker, A.R.; Song, X.; Wang, X.; Wendt, M.D.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J. Med. Chem., 2007, 50(4), 641-662.
107. Park, C.M.; Bruncko, M.; Adickes, J.; Bauch, J.; Ding, H.; Kunzer, A.; Marsh, K.C.; Nimmer, P.; Shoemaker, A.R.; Song, X.; Tahir, S.K.; Tse, C.; Wang, X.; Wendt, M.D.; Yang, X.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins. J. Med. Chem., 2008, 51(21), 6902-6915.
108. Chen, H.; Yang, Z.; Ding, C.; Chu, L.; Zhang, Y.; Terry, K.; Liu, H.; Shen, Q.; Zhou, J. Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy. Eur. J. Med. Chem., 2013, 62, 498-507.
109. Yu, W.; Xiao, H.; Lin, J.; Li, C. Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design. J. Med. Chem., 2013, 56(11), 4402-4412.
110. Crawford, T.D.; Ndubaku, C.O.; Chen, H.; Boggs, J.W.; Bravo, B.J.; DeLaTorre, K.; Giannetti, A.M.; Gould, S.E.; Harris, S.F.; Magnuson, S.R. Discovery of selective 4-amino-pyridopyrimidine inhibitors of MAP4K4 using fragment-based lead identification and optimization. J. Med. Chem., 2014, 57(8), 3484-3493.
111. Howard, S.; Amin, N.; Benowitz, A.B.; Chiarparin, E.; Cui, H.; Deng, X.; Heightman, T.D.; Holmes, D.J.; Hopkins, A.; Huang, J. Fragment-based discovery of 6-azaindazoles as inhibitors of bacterial DNA ligase. ACS Med. Chem. Lett., 2013, 4(12), 1208-1212.
112. Kathman, S.G.; Xu, Z.; Statsyuk, A.V. A fragment-based method to discover irreversible covalent inhibitors of cysteine proteases. J. Med. Chem., 2014, 57(11), 4969-4974.
113. Ning, W.; Zhu, J.; Zheng, C.; Liu, X.; Song, Y.; Zhou, Y.; Zhang, X.; Zhang, L.; Sheng, C.; Lv, J. Fragment-based design of novel quinazolinon derivatives as human zcrosin inhibitors. Chem. Biol. Drug Des., 2013, 81(4), 437-441.
114. Frett, B.; Moccia, M.L.; Carlomagno, F.; Santoro, M.; Li, H.Y. Identification of two novel RET kinase inhibitors through MCRbased drug discovery: Design, synthesis and evaluation. Eur. J. Med. Chem., 2014, 86, 714-723.
115. Saxty, G.; Norton, D.; Affleck, K.; Clapham, D.; Cleasby, A.; Coyle, J.; Day, P.; Frederickson, M.; Hancock, A.; Hobbs, H. Identification of orally bioavailable small-molecule inhibitors of hematopoietic prostaglandin D2 synthase using X-ray fragment based drug discovery. Med. Chem. Comm., 2014, 5, 134-141.
116. Johnson, C.N.; Berdini, V.; Beke, L.; Bonnet, P.; Brehmer, D.; Coyle, J.E.; Day, P.J.; Frederickson, M.; Freyne, E.J.; Gilissen, R.A. Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase. ACS Med. Chem. Lett., 2014, DOI: 10.1021/ml5001245.
117. Caliandro, R.; Belviso, D.B.; Aresta, B.M.; Candia, M.d.; Altomare, C.D. Protein crystallography and fragment-based drug design. Future Med. Chem., 2013, 5(10), 1121-1140.