Drugging challenging targets using fragment-based approaches

Current Opinion in Chemical Biology

Volumn 14, Issue 3, 2010, Pages 299-307

  Coyne, Anthony G ^a   Scott, Duncan E ^a   Abell, Chris ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA SECRETASE; BIOTIN CARBOXYLASE; CARBOXYLASE; DNA BINDING PROTEIN; E2 TRANSCRIPTION FACTOR; HEAT SHOCK PROTEIN 90; PROTEIN BCL XL; RNA POLYMERASE; THROMBIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

CHEMICAL STRUCTURE; COMPUTER MODEL; FRAGMENTATION REACTION; HUMAN; IC 50; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REVIEW; VIRUS REPLICATION;

COMPUTER SIMULATION; DNA-BINDING PROTEINS; DNA-DIRECTED RNA POLYMERASES; DRUG DISCOVERY; HUMANS; PROTEIN INTERACTION MAPPING; SMALL MOLECULE LIBRARIES;

EID: 77952546241     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbpa.2010.02.010     Document Type: Review

References (56)

1. Chessari G., and Woodhead A.J. From fragment to clinical candidate - a historical perspective. Drug Discov Today 14 (2009) 668-675
2. Murray C.W., and Rees D. The rise of fragment-based drug discovery. Nat Chem 1 (2009) 187-192. This review gives an excellent outline of the development of fragment-based drug discovery.
3. de Kloe G., Bailey D., Leurs R., and de Esch I. Transforming fragments into candidates: small becomes big in medicinal chemistry. Drug Discov Today 14 (2009) 630-646
4. Jahnke W., and Erlanson D.A. In: Mannhold R., Kubinyi H., and Folkers G. (Eds). Fragment Based Approaches in Drug Discovery (Methods and Principles in Medicinal Chemistry) (2006), Wiley-VCH
5. In: Zartler E., and Shapiro M. (Eds). Fragment Based Drug Discovery: A Practical Approach (2008), Wiley Blackwell
6. Bembenek S.D., Tounge B.A., and Reynolds C.H. Ligand efficiency and fragment-based drug discovery. Drug Discov Today 14 (2009) 278-283
7. Hopkins A.L., Groom C.R., and Alex A. Ligand efficiency: a useful metric for lead selection. Drug Discov Today 9 (2004) 430-431
8. Ciulli A., Williams G., Smith A.G., Blundell T.L., and Abell C. Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods. J Med Chem 49 (2006) 4992-5000
9. Lundqvist T. The devil is still in the details - driving early drug discovery forward with biophysical experimental methods. Curr Opin Drug Discov Dev 8 (2005) 513-519
10. Hesterkamp T., Barker J., Davenport A., and Whittaker M. Fragment based drug discovery using fluorescence correlation spectroscopy techniques: challenges and solutions. Curr Top Med Chem 7 (2007) 1582-1591
11. Ward W.H., and Holdgate G.A. Isothermal titration calorimetry in drug discovery. Prog Med Chem 38 (2001) 309-376
12. Klages J., Coles M., and Kessler H. NMR-based screening: a powerful tool in fragment-based drug discovery. Analyst 132 (2007) 693-705
13. 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., et al. Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR. J Am Chem Soc 119 (1997) 5818-5827
14. Shuker S.B., Hajduk P.J., Meadows R.P., and Fesik S.W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 274 (1996) 1531-1534
15. Blundell T.L., Jhoti H., and Abell C. High-throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov 1 (2002) 45-54
16. Jhoti H., Cleasby A., Verdonk M., and Williams G. Fragment-based screening using X-ray crystallography and NMR spectroscopy. Curr Opin Chem Biol 11 (2007) 485-493
17. Muchmore S.W., and Hajduk P.J. Crystallography, NMR and virtual screening: integrated tools for drug discovery. Curr Opin Drug Discov Dev 6 (2003) 544-549
18. Hajduk P.J., Huth J.R., and Fesik S.W. Druggability indices for protein targets derived from NMR-based screening data. J Med Chem 48 (2005) 2518-2525
19. Siegal G., Ab E., and Schultz J. Integration of fragment screening and library design. Drug Discov Today 12 (2007) 1032-1039
20. Hadjuk P.J., Gomtsyan A., Didomenico S., Cowart M., Bayburt E.K., Solomon L., Severin J., Smith R., Walter K., Holzman T.F., et al. Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J Med Chem 43 (2000) 4780-4786
21. Gill A., Cleasby A., and Jhoti H. The discovery of novel protein kinase inhibitors by using fragment-based high-throughput X-ray crystallography. ChemBioChem 6 (2005) 506-512
22. Liu G., Xin Z.L., Pei Z.G., Hajduk P.J., Abad-Zapatero C., Hutchins C.W., Zhao H.Y., Lubben T.H., Ballaron S.J., Haasch D.L., et al. Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor. J Med Chem 46 (2003) 4232-4235
23. Antonysamy S., Hirst G., Park F., Sprengeler P., Stappenbeck F., Steensma R., Wilson M., and Wong M. Fragment-based discovery of JAK-2 inhibitors. Bioorg Med Chem Lett 19 (2009) 279-282
24. Mpamhanga C.P., Spinks D., Tulloch L.B., Shanks E.J., Robinson D.A., Collie I.T., Fairlamb A.H., Wyatt P.G., Frearson J.A., Hunter W.N., et al. One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening. J Med Chem 52 (2009) 4454-4465
25. Chung F., Tisne C., Lecourt T., Seijo B., Dardel F., and Micouin L. Design of tRNA(3)(Lys) ligands: fragment evolution and linker selection guided by NMR spectroscopy. Chem Eur J 15 (2009) 7109-7116
26. Hohwy M., Spadola L., Lundquist B., Hawtin P., Dahmen J., Groth-Clausen I., Nilsson E., Persdotter S., Von Wachenfeldt K., Folmer R.H.A., et al. Novel prostaglandin d synthase inhibitors generated by fragment-based drug design. J Med Chem 51 (2008) 2178-2186
27. Howard N., Abell C., Blakemore W., Chessari G., Congreve M., Howard S., Jhoti H., Murray C.W., Seavers L.C., and van Montfort R.L. Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors. J Med Chem 49 (2006) 1346-1355
28. Geschwindner S., Olsson L.L., Albert J.S., Deinum J., Edwards P.D., de Beer T., and Folmer R.H. Discovery of a novel warhead against beta-secretase through fragment-based lead generation. J Med Chem 50 (2007) 5903-5911
29. Arkin M.R., and Wells J.A. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov 3 (2004) 301-317
30. Yin H., and Hamilton A.D. Strategies for targeting protein-protein interactions with synthetic agents. Angew Chem Int Ed 44 (2005) 4130-4163
31. Wells J.A., and McClendon C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450 (2007) 1001-1009. Excellent review on the targeting of protein-protein interactions using small molecules.
32. 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., et al. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-x(L) from NMR and parallel synthesis. J Med Chem 49 (2006) 656-663. This paper describes the use of SAR by NMR for FBDD. This work provides a good example of fragment linking.
33. Park C.M., Bruncko M., Adickes J., Bauch J., Ding H., Kunzer A., Marsh K.C., Nimmer P., Shoemaker A.R., Song X., et al. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins. J Med Chem 51 (2008) 6902-6915
34. Taldone T., Sun W., and Chiosis G. Discovery and development of heat shock protein 90 inhibitors. Bioorg Med Chem 17 (2009) 2225-2235
35. Sgobba M., and Rastelli G. Structure-based and in silico design of Hsp90 inhibitors. ChemMedChem 4 (2009) 1399-1409
36. Barker J.J., Barker O., Boggio R., Chauhan V., Cheng R.K., Corden V., Courtney S.M., Edwards N., Falque V.M., Fusar F., et al. Fragment-based identification of Hsp90 inhibitors. ChemMedChem 4 (2009) 963-966
37. Huth J.R., Park C., Petros A.M., Kunzer A.R., Wendt M.D., Wang X., Lynch C.L., Mack J.C., Swift K.M., Judge R.A., et al. Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies. Chem Biol Drug Discov 70 (2007) 1-12
38. Brough P.A., Barril X., Borgognoni J., Chene P., Davies N.G., Davis B., Drysdale M.J., Dymock B., Eccles S.A., Garcia-Echeverria C., et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem 52 (2009) 4794-4809
39. Gordon C.P., and Keller P.A. Control of hepatitis C: a medicinal chemistry perspective. J Med Chem 48 (2005) 1-20
40. Hirashima S., Suzuki T., Ishida T., Noji S., Yata S., Ando I., Komatsu M., Ikeda S., and Hashimoto H. Benzimidazole derivatives bearing substituted biphenyls as hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors: structure-activity relationship studies and identification of a potent and highly selective inhibitor JTK-109. J Med Chem 49 (2006) 4721-4736
41. Antonysamy S.S., Aubol B., Blaney J., Browner M.F., Giannetti A.M., Harris S.F., Hebert N., Hendle J., Hopkins S., Jefferson E., et al. Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors. Bioorg Med Chem Lett 18 (2008) 2990-2995. This paper examines an X-ray crystallography fragment-based approach to targeting HCV NS5B.
42. Chan L., Pereira O., Reddy T.J., Das S.K., Poisson C., Courchesne M., Proulx M., Siddiqui A., Yannopoulos C.G., Nguyen-Ba N., et al. Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCVNS5B polymerase and HCV subgenomic RNA replication. Part 2: tertiary amides. Bioorg Med Chem Lett 14 (2004) 797-800
43. 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., et al. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein. J Med Chem 40 (1997) 3144-3150
44. Liang H., Petros A.M., Meadows R.P., Yoon H.S., Egan D.A., Walter K., Holzman T.F., Robins T., and Fesik S.W. Solution structure of the DNA-binding domain of a human papillomavirus E2 protein: evidence for flexible DNA-binding regions. Biochemistry 35 (1996) 2095-2103
45. Kim S.S., Tam J.K., Wang A.F., and Hegde R.S. The structural basis of DNA target discrimination by papillomavirus E2 proteins. J Biol Chem 275 (2000) 31245-31254
46. Dullweber F., Stubbs M.T., Musil D., Sturzebecher J., and Klebe G. Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition. J Mol Biol 313 (2001) 593-614
47. Matsuo T., Koide M., and Kario K. Development of argatroban, a direct thrombin inhibitor, and its clinical application. Semin Thromb Hemost 23 (1997) 517-522
48. Rees D.C., Congreve M., Murray C.W., and Carr R. Fragment-based lead discovery. Nat Rev Drug Discov 3 (2004) 660-672
49. Hardy J., and Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297 (2002) 353-356
50. Hong L., Koelsch G., Lin X., Wu S., Terzyan S., Ghosh A.K., Zhang X.C., and Tang J. Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor. Science 290 (2000) 150-153
51. Edwards P.D., Albert J.S., Sylvester M., Aharony D., Andisik D., Callaghan O., Campbell J.B., Carr R.A., Chessari G., Congreve M., et al. Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency. J Med Chem 50 (2007) 5912-5925
52. Congreve M., Aharony D., Albert J., Callaghan O., Campbell J., Carr R.A., Chessari G., Cowan S., Edwards P.D., Frederickson M., et al. Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase. J Med Chem 50 (2007) 1124-1132
53. Murray C.W., Callaghan O., Chessari G., Cleasby A., Congreve M., Frederickson M., Hartshorn M.J., McMenamin R., Patel S., and Wallis N. Application of fragment screening by X-ray crystallography to beta-secretase. J Med Chem 50 (2007) 1116-1123
54. Payne D.J., Gwynn M.N., Holmes D.J., and Pompliano D.L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 6 (2007) 29-40
55. Zhang Y.M., White S.W., and Rock C.O. Inhibiting bacterial fatty acid synthesis. J Biol Chem 281 (2006) 17541-17544
56. Mochalkin I., Miller J.R., Narasimhan L., Thanabal V., Erdman P., Cox P.B., Prasad J.V.N.V., Lightle S., Huband M.D., and Stover C.K. Discovery of antibacterial biotin carboxylase inhibitors by virtual screening and fragment-based approaches. ACS Chem Biol 4 (2009) 473-483