Targeting neurodegenerative diseases: Drug discovery in a challenging arena

Pure and Applied Chemistry

Volumn 84, Issue 7, 2012, Pages 1543-1556

  Abou Gharbia, Magid ^a   Childers, Wayne ^a  

^a TEMPLE UNIVERSITY   (United States)

Author keywords

Alzheimer's; BACE1; Bioactive molecules; Bioorganic chemistry; Computer aided molecular design; Enzyme ILS 920; Immunophilin; Inhibitors; Macromolecular chemistry; Medicinal chemistry; Stroke; WAY 258,131

Indexed keywords

ALZHEIMER'S; BACE1; BIOACTIVE MOLECULES; BIOORGANIC CHEMISTRY; COMPUTER AIDED MOLECULAR DESIGN; IMMUNOPHILINS; MACROMOLECULAR CHEMISTRY; MEDICINAL CHEMISTRY; STROKE; WAY-258,131;

BIOCHEMISTRY; CORROSION INHIBITORS; HEALTH CARE; SYNTHESIS (CHEMICAL);

NEURODEGENERATIVE DISEASES;

EID: 84863752621     PISSN: 00334545     EISSN: 13653075     Source Type: Journal    
DOI: 10.1351/PAC-CON-11-11-09     Document Type: Article

References (46)

1. S. Saxena, P. Caroni. Neuron 71, 35 (2011).
2. For a recent review, see: N. Herrmann, S. A. Chau, I. Kircanski, K. L. Lanctot. Drugs 71, 2031 (2011).
3. X.-P. Wang, H.-L. Ding. Neurosci. Bull. 24, 105 (2008).
4. A. Wimo, M. Prince. World Alzheimer Report 2010, Alzheimer's Disease International, available online at: .
5. G. M. Shanker, D. M. Walsh. Mol. Neurodegen. (2009). Available online at: .
6. For a recent review, see: A. D. Korczyn. Alzheimer's Dementia 4, 176 (2008).
7. K. G. Mawuenyega, W. Sigurnson, V. Ovod, L. Munsell, T. Kasten, J. C. Morris, K. E. Yarasheski, R. J. Bateman. Science 330, 1774 (2010).
8. N. Marks, M. J. Berg. Neurochem. Res. 35, 181 (2010).
9. A. F. Kreft, R. Martone, A. Porte. J. Med. Chem. 52, 6169 (2009).
10. W.-H. Huang, R. Sheng, Y.-A. Hu. Curr. Med. Chem. 16, 1806 (2009).
11. B. P. Imbimbo, I. Peretto. Curr. Opin. Invest. Drugs 10, 721 (2009).
12. Eli Lilly Press Release, 17 August 2010, accessed on 14 October 2011 at: .
13. S. C. Mayer, A. F. Kreft, B. Harrison, M. Abou-Gharbia, M. Antane, S. Aschmies, K. Atchison, M. Chlenov, D. C. Cole, T. Comery, G. Diamantidis, J. Ellingboe, K. Fan, R. Galante, C. Gonzales, D. M. Ho, M. E. Hoke, Y. Hu, D. Huryn, U. Jain, M. Jin, K. Kremer, D. Kubrak, M. Lin, P. Lu, R. Magolda, R. Martone, W. Moore, A. Oganesian, M. N. Pangalos, A. Porte, P. Reinhart, L. Resnick, D. R. Riddell, J. Sonnenberg-Reines, J. R. Stock, S.-C. Sun, E. Wagner, T. Wang, K. Woller, Z. Xu, M. M. Zaleska, J. Zeldis, M. Zhang, H. Zhou, J. S. Jacobsen. J. Med. Chem. 51, 7348 (2008).
14. A. Hall, R. L. Elliot, G. M. P. Giblin, I. Hussain, J. Musgrave, A. Naylor, R. Sasse, B. Smith. Bioorg. Med. Chem. Lett. 20, 1306 (2010).
15. W.-H. Huang, R. Sheng, H.-A. Hu. Curr. Med. Chem. 16, 1806 (2009).
16. M. S. Malamas, J. Erdei, I. Gunawan, K. Barnes, M. Johnson, Y. Hui, J. Turner, Y. Hu, E. Wagner, K. Fan, A. Olland, J. Bard, A. J. Robichaud. J. Med. Chem. 52, 6314 (2009).
17. P. Wu, L. Brand. Anal. Biochem. 218, 1 (1994).
18. I. Schechter, E. Ziv. Biol. Chem. 389, 313 (2008).
19. M. S. Malamas, J. Erdei, I. Gunawan, J. Turner, Y. Hu, E. Wagner, K. Fan, R. Chopra, A. Olland, J. Bard, S. Jacobsen, R. L. Magolda, M. Pangalos, A. J. Robichaud. J. Med. Chem. 53, 1146 (2010).
20. K. Hsiao, P. Chapman, S. Nilson, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole. Science 274, 99 (1996).
21. T. A. Comery, R. L. Martone, S. Aschmies, K. P. Atchison, G. Diamantidis, X. Gong, H. Zhou, A. F. Kreft, M. N. Pangalos, J. Sonnenberg-Reines, J. S. Jacobsen, K. L. Marquis. J. Neurosci. 25, 8898 (2005).
22. World Health Organization. "STEPwise approach to stroke surveillance", accessed online on 14 October 2011 at: .
23. H. P. Adams Jr., G. del Zoppo, J. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, P. D. Lyden, L. B. Morgenstern, A. I. Qureshi, R. H. Rosenwasser, P. A. Scott, E. F. M. Wijdicks. Stroke 38, 1655 (2007).
24. J. Kaur, Z. Zhao, G. M. Kline, E. H. Lao, A. M. Buchan. J. Cereb. Blood Flow Metab. 24, 945 (2004).
25. V. E. O'Collins, M. R. Macleod, G. A. Donnan, L. L. Horky, B. H. van der Worp, D. W. Howells. Ann. Neurol. 59, 467 (2006).
26. H. T. Ghashghaei, C. Lai, E. S. Anton. Nat. Rev. Neurosci. 8, 141 (2007).
27. A. M. Enciu, M. I. Nicolescu, C. G. Manole, D. F. Muresanu, L. M. Popescu, B. O. Popescu. BMC Neurol. 11, 75 (2011).
28. G. Pyne-Geithman. Neurology 74, 352 (2010).
29. M. M. Zaleska, M. L. T. Mercado, J. Chavez, G. Z. Feuerstein, M. N. Pangalos, A. Wood. Neuropharmacology 56, 329 (2009).
30. C. Vezina, A. Kudelski, S. N. Sehgal. J. Antibiot. 28, 721 (1975).
31. S. N. Sehgal. Clin. Biochem. 31, 335 (1998).
32. N. Hay, N. Sonenberg. Genes Dev. 18, 1926 (2004).
33. S. Wullschleger, R. Loewith, M. N. Hall. Cell 124, 471 (2006).
34. J. Choi, J. Chen, S. L. Schreiber, J. Clardy. Science 273, 239 (1996).
35. W. E. Lyons, E. B. George, T. M. Dawson, J. P. Steiner, S. H. Snyder. Proc. Nat. Acad. Sci. USA 94, 3191 (1994).
36. M. Y. Summers, M. Leighton, D. Liu, K. Pong, E. I. Graziani. J. Antibiot. 59, 184 (2006).
37. D. Liu, B. McIlvain, M. Fennell, J. Dunlop, A. Wood, M. M. Zaleska, E. I. Graziani, K. Pong. J. Neurosci. Meth. 163, 310 (2007).
38. E. Graziani. In RSC Drug Discovery Series, #4. Accounts in Drug Discovery: Case Studies in Medicinal Chemistry, J. C. Barrish, P. H. Carter, P. T. W. Cheng, R. Zohler (Eds.), pp. 316-330, RCS Publishing, London (2011).
39. Neuronal survival was determined by measuring neurofilament content in cultured rat cortical neurons using an ELISA assay.
40. T. D. Ocain, K. Longhi, R. J. Steffan, R. G. Caccese, S. N. Sehgal. Biochem. Biophys. Res. Commun. 192, 1340 (1993).
41. In vitro immunosuppression was measured as the inhibition of IL-2-stimulated human CD4+ T cell proliferation.
42. M. Abou-Gharbia. J. Med. Chem. 52, 2 (2009).
43. B. Ruan, K. Pong, F. Jow, M. Bowlby, R. A. Crozier, D. Liu, S. Liang, Y. Chen, M. L. Mercado, X. Feng, F. Bennett, D. von Schack, L. McDonald, M. M. Zaleska, A. Wood, P. H. Reinhart, R. L. Magolda, J. Skotnicki, M. N. Pangalos, F. E. Koehn, G. T. Carter, M. Abou-Gharbia, E. I. Graziani. Proc. Natl. Acad. Sci. USA 105, 33 (2008).
44. J. Sharkey, S. P. Butcher. Nature 371, 336 (1994).
45. Manuscript in preparation.
46. B. G. Gold, V. Densmore, W. Shou, M. M. Matzuk, H. S. Gordon. J. Pharmacol. Exp. Ther. 289, 1202 (1999).