Human β-Secretase (BACE) and BACE Inhibitors

Journal of Medicinal Chemistry

Volumn 46, Issue 22, 2003, Pages 4625-4630

  John, Varghese ^a   Beck, James P ^b   Bienkowski, Michael J ^b   Sinha, Sukanto ^a   Heinrikson, Robert L ^b  

^a ELAN PHARMACEUTICALS   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SECRETASE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; BETA SECRETASE INHIBITOR; ENZYME INHIBITOR; GAMMA SECRETASE; OM 992; PEPTIDE DERIVATIVE; PHOSPHINYLSUCCINIC ACID DERIVATIVE; PHOSPHORYLMETHYLSUCCINIC ACID; STATINE DERIVATIVE; TETRALIN DERIVATIVE; TETRAPEPTIDE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; CARBOXY TERMINAL SEQUENCE; CONCENTRATION RESPONSE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TARGETING; ENZYME BINDING; ENZYME INHIBITION; ENZYME ISOLATION; ENZYME KINETICS; ENZYME MECHANISM; ENZYME PURIFICATION; ENZYME STRUCTURE; ENZYME SUBSTRATE; GENETIC TRANSFECTION; HUMAN; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PROCESSING; PROTEIN TARGETING; PROTEIN TERTIARY STRUCTURE; SHORT SURVEY; STRUCTURE ACTIVITY RELATION;

AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ENDOPEPTIDASES; ENDOPEPTIDASES; HUMANS; MOLECULAR MIMICRY; PROTEASE INHIBITORS;

EID: 0142092495     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030247h     Document Type: Short Survey

References (43)

1. Glenner, G. G.; Wong, C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984, 120, 885-890.
2. Vassar, R.; Bennett, B. D.; Babu-Khan, S.; Kahn, S.; Mendiaz, E. A.; Denis, P.; Teplow, D. B.; Ross, S.; Amarante, P.; Loeloff, R.; Luo, Y.; Fisher, S.; Fuller, J.; Edenson, S.; Lile, J.; Jarosinski, M. A.; Biere, A. L.; Curran, E.; Burgess, T.; Louis, J.-C.; Collins, F.; Treanor, J.; Rogers, G.; Citron, M. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999, 286, 735-741.
3. Yan, R.; Bienkowski, M. J.; Shuck, M. E.; Miao, H.; Tory, M. C.; Pauley, A. M.; Brashier, J. R.; Stratman, N. C.; Mathews, W. R.; Buhl, A. E.; Carter, D. B.; Tomasselli, A. G.; Parodi, L. A.; Heinrikson, R. L.; Gurney, M. E. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 1999, 402, 533-537.
4. Sinha, S.; Anderson, J. P.; Barbour, R.; Basi, G. S.; Caccavello, R.; Davis, D.; Doan, M.; Dovey, H. F.; Frigon, N.; Hong, J.; Jacobson-Croak, K.; Jewett, N.; Keim, P.; Knops, J.; Lieberburg, I.; Power, M.; Tan, H.; Tatsuno, G.; Tung, J.; Schenk, D.; Seubert, P.; Suomensaari, S. M.; Wang, S.; Walker, D. ; Zhao, J.; McConlogue, L.; John, V. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 1999, 402, 537-540.
5. Cai, H.; Wang, Y.; McCarthy, D.; Wen, H.; Borchelt, D. R.; Price, D. L.; Wong, P. C. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat. Neurosci. 2001, 4, 233-234.
6. Yan, R.; Han, P.; Miao, H.; Greengard, P.; Xu, H. The transmembrane domain of the Alzheimer's β-secretase (BACE1) determines its late Golgi localization and access to β-amyloid precursor protein (APP) substrate. J. Biol. Chem. 2001, 276, 36788-36796.
7. Shi, X.-P.; Chen, E.; Yin, K.-C.; Na, S.; Garsky, V. M.; Lai, M.-T.; Li, Y.-M.; Platchek, M.; Register, R. B.; Sardana, M. K.; Tang, M.-J.; Thiebeau, J. ; Wood, T.; Shafer, J.; Gardell, S. J. The pro domain of β-secretase does not confer strict zymogen-like properties but assists proper refolding of the protease domain. J. Biol. Chem. 2001, 267, 10366-10373.
8. Roberds, S. L.; Anderson, J.; Basi, G.; Bienkowski, M. J.; Branstetter, D. G.; Chen, K. S.; Freedman, S.; Frigon, N. L.; Games, D.; Hu, K.; Johnson-Wood, K.; Kappenman, K. E.; Kawabe, T.; Kola, I.; Kuehn, R.; Lee, M.; Liu, W.; Motter, R.; Nichols, N. F.; Power, M.; Robertson, D. W.; Schenk, D.; Schoor, M.; Shopp, G. M.; Shuck, M. E.; Sihna, S.; Svensson, K. A.; Tatsuno, G. ; Tintrup, H.; Wijsman, J.; Wright, S.; McConlogue, L. BACE knockout mice are healthy despite lacking the primary β-secretase activity in the brain: implications for Alzheimer's disease therapeutics. Hum. Mol. Genet. 2001, 10, 1317-1324.
9. Huse, J. T.; Pijak, D. S.; Leslie, G. J.; Lee, V. M.; Doms, R. W. Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer's disease beta-secretase. J. Biol. Chem. 2000, 275, 33729-33737.
10. Bennett, B. D.; Denis, P.; Haniu, M.; Teplow, D. B.; Kahn, S.; Louis, J. C.; Citron, M.; Vassar, R. A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta-secretase. J. Biol. Chem. 2000, 275, 37712-37717.
11. Acquati, F.; Accarino, M.; Nucci, C.; Fumagalli, P.; Jovine, L.; Ottolenghi, S.; Taramelli, R. The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region. FEBS Lett. 2000, 468, 59-64.
12. Sisodia, S. S.; Koo, E. H.; Beyreuther, K.; Unterbeck, A.; Price, D. Evidence that the β-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 1990, 248, 492-495.
13. Esler, W. P.; Wolfe, M. S. A portrait of Alzheimer secretases-New features and familiar faces. Science 2001, 293, 1449-1454.
14. (a) Sisodia, S. S.; St. George-Hyslop, P. H. γ-Secretase, Notch, Aβ and Alzheimer's disease: where do the presenilins fit in? Nat. Rev. Neurosci. 2002, 3, 281-289.
15. (b) Schmidt B. Aspartic proteases involved in Alzheimer's disease. ChemBioChem 2003, 4, 366-378.
16. Hong, L.; Koelsch, G.; Lin, X.; Wu, S.; Terzyan, S.; Ghosh, A. K.; Zhang, X. C.; Tang, J. Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science 2000, 290, 150-153.
17. Ghosh, A. K.; Bilcer, G.; Harwood, C.; Kawahama, R.; Shin, D.; Hussain, K. A.; Hong, L.; Loy, J. A.; Nguyen, C.; Koelsch, G.; Ermolieff, J.; Tang, J. Structure-Based Design: Potent Inhibitors of Human Brain Memapsin 2 (β-secretase). J. Med. Chem. 2001, 44, 2865-2868.
18. Tung, J. S.; Davis, D. L.; Anderson, J. P.; Walker, D. E.; Mamo, S.; Jewett, N. E.; Hom, R. K.; Sinha, S.; Thorsett, E. D.; John, V. Design of substrate-based inhibitors of human β-secretase. J. Med. Chem. 2002, 45, 259-262.
19. Hom, R. K.; Fang, L. Y.; Mamo, S.; Tung, J. S.; Guinn, A. C.; Walker, D. E.; Davis, D. L.; Gailunas, A. F.; Thorsett, E. D.; Sinha, S.; Knops, J. E.; Jewett, N. E.; Anderson, J. P.; John, V. Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human β-secretase. J. Med. Chem. 2003, 46, 1799-1802.
20. (a) John, V.; Tung, J.; Fang, L.; Mamo, S. S. Patent WO 00/077030, 2000.
21. (b) Hom, R.; Mamo, S.; Tung, J.; Gailunas, A.; John, V.; Fang, L. Patent WO 01/070672, 2001.
22. (c) Fang, L. Y.; Hom, R.; John, V.; Maillaird, M. Patent WO 02/002505, 2002.
23. (d) Fang, L. Y.; John, V. Patent WO 02/002506, 2002.
24. (e) Maillaird, M.; Hom, R.; Gailunas, A.; Jagodzinska, B.; Fang, L. Y.; John, V.; Freskos, J. N.; Pulley, S. R.; Beck, J. P.; TenBrink, R. E. Patent WO 02/002512, 2002.
25. (f) Beck, J. P.; Gailunas, A.; Hom, R.; Jagodzinska, B.; John, V.; Maillaird, M. Patent WO 02/002520, 2002.
26. (g) Schostarez, H.; Chrusciel, R. A.; Centko, R. S. Patent WO 02/094768, 2002.
27. (h) Freskos, J. N.; Aquino, J.; Brown, D. L.; Fang, L.; Fobian, Y. M.; Gailunas, A.; Guinn, A.; John, V.; Romero, A. G.; Tucker, J.; Tung, J.; Walker, D. Patent WO 02/098849, 2002.
28. (i) Pulley, S. R.; Beck, J. P.; TenBrink, R. E.; Jacobs, J. S. Patent WO 02/100399, 2002.
29. (j) Schostarez, H. J.; Chrusciel, R. A. Patent WO 02/100818, 2002.
30. (k) Maillaird, M.; Tucker, J. A. Patent WO 02/100820, 2002.
31. (l) Pulley, S. R.; Beck, J. P.; TenBrink, R. E. Patent WO 02/100856, 2002.
32. (m) John, V.; Hom, R.; Tucker, J. Patent WO 03/002122, 2003.
33. (n) Schostarez, H. J.; Chrusciel, R. A. Patent WO 03/ 006013, 2003.
34. (o) Schostarez, H. J.; Chrusciel, R. A. Patent WO 03/006021, 2003.
35. (p) Gailunas, A.; Hom, R.; John, V.; Maillard, M.; Chrusciel, R. A.; Fisher, J.; Jacobs, J.; Freskos, J. N.; Brown, D. L.; Fobian, Y. M. Patent WO 03/006423, 2003.
36. (q) Schostarez, J. H.; Chrusciel, R. A. Patent WO 03/006453, 2003.
37. (r) Gailunas, A.; Tucker, J. A.; John, V. Patent WO 03/027068, 2003.
38. (s) Fisher, J. F.; Jacobs, J. S.; Sherer, B. A. Patent WO 03/029169, 2003.
39. (a) Tang, J. N.; Koelsch, G.; Ghosh, A. K. Patent WO 02/53594, 2002.
40. (b) Tang, J. J. N.; Hong, L.; Ghosh, A. K. Patent WO 01/ 00665, 2001.
41. Miyamoto, M.; Matsui, J.; Fukumoto, H.; Tarui, N. Patent WO 01/187293, 2001.
42. Qiao, L.; Etcheberrigaray, R. Patent WO 02/96897, 2002.
43. Bhisetti, G. R.; Saunders, J. O.; Murcko, M. A.; Lepre, C. A.; Britt, S. D.; Come, J. H.; Deninger, D. D.; Wang, T. Patent WO 02/88101, 2002.